Guest guest Posted April 25, 2008 Report Share Posted April 25, 2008 A long article about the 5ht1a receptors, the 5ht2a receptors, and the roles in sleep and wakefullness. I'd just like to reiterate that these theories about teh 5ht1a/5ht2a receptors and problems sleep archiatecture is not just some " wacky " idea. The fact that it has produced so many significant results - MDMA/nutmeg/sleep deprivation etc. is probably not mere coincidence. Sentences in this view contain interactions of HTR1A - Interaction Information is available whenever you see this symbol - Read more. For a summary overview of the information in this page click here. Show allHigh impact journalsExperimentally confirmed Order by relevanceOrder by dateOrder by PMID Notably, it has been reported that 5-HT1A/B receptors are involved in the regulation of rapid eye movement sleep (REMS) and that 5-HT2A/C receptors participate in the control of slow wave sleep (SWS), but the role of 5-HT3 receptors is less well characterised. [2001] Ipsapirone, a 5-HT1A agonist, suppresses REM sleep equally in unmedicated depressed patients and normal controls. [1996] To determine whether ipsapirone, a 5-HT1A agonist, differentially suppresses REM sleep in depressed patients compared with normal controls, we administered placebo, ipsapirone 10 mg, or ipsapirone 20 mg in a double-blind, random order before bedtime in 18 unmedicated patients with depression and 16 age-matched, gender-matched normal controls. [1996] Systemic administration of 5-HT1A agonists consistently increases wakefulness, whereas slow wave sleep (SWS) and REM (rapid-eye movement) sleep are reduced. [1998] These complex sleep/wake data of 5-HT1A ligands suggest that 5-HT1A receptor activation may increase waking, increase slow wave sleep or increase REM sleep depending on where the 5-HT1A receptors are located within the central nervous system. [1998] Systemic administration of the selective 5-HT1A receptor agonist 8- OHDPAT induces dose-dependent effects; i.e. low doses increase slow wave sleep and reduce waking, whereas large doses increase waking and reduce slow wave sleep and REM sleep. [2000] The REM sleep-suppressing effect of postsynaptic 5-HT1A stimulation has been well established. [1996] Direct injection of a selective 5-HT1A agonist into the pedunculopontine tegmental nuclei reduces REM sleep, consistent with such a hypothesis. [1998] Microdialysis perfusion of a selective 5-HT1A agonist into the dorsal Raphe nucleus causes an increase in REM sleep, whereas the other sleep/wake stages are unaltered. [1998] The 5-HT1A agonist ipsapirone enhances EEG slow wave activity in human sleep and produces a power spectrum similar to 5-HT2 blockade. [1996] In view of evidence that 5HT2A and 5HT2C sites functionally interact with 5HT1A receptors, we also examined the influence of these agents upon the actions of S 15535, but no significant alteration was seen in its enhancement of rhythms. [2006] Lower brainstem serotonin and 5-hydroxyindoleacetic acid, fewer prefrontal serotonin transporter (5-HTT) sites and more post-synaptic 5-HT1A and 5HT2A receptors were reported in suicide. [2006] The mechanism whereby chronic stress, via the CRF induced activation of the dorsal raphe nucleus, can induce a change in the serotonergic system, involves an increase in the 5HT2A and a decrease in the 5HT1A receptor mediated function. [2005] At a receptor level, chronic treatment with hypericum downregulates beta1-adrenoceptor, upregulates post-synaptic 5-HT1A receptors and 5- HT2 receptors. [2001] In this study, we examined the expression of 5HT1A, 5HT2A, 5HT2C receptors and GAD67 in the hypothalamus of SS, HSR and MSR monkeys using in situ hybridization. [2007] Glucocorticoid receptor [?]-dependent desensitization of 5-HT1A [?] autoreceptors by sleep deprivation: studies in GR-i transgenic mice. [2006] Distinct temporal pattern of the effects of the combined serotonin- reuptake inhibitor and 5-HT1A agonist EMD 68843 on the sleep EEG in healthy men. [2001] CONCLUSIONS: These data suggest that glucocorticoid-receptor [?] activation by corticosterone participates in the antidepressant-like adaptive changes in 5-HT1A [?] autoreceptors in sleep-deprived mice. [2006] This hypothesis was tested by ascertaining the ability of anti- idiotypic antibodies to immunostain cells transfected in vitro with cDNA encoding the 5-HT1C or 5-HT2 receptor or with a genomic clone encoding the 5-HT1A receptor. [1991] In addition, some 5-HT1A receptor-mediated responses are known to be potentiated by co-administration of 5-HT2A receptor antagonists. [1996] top The increased 5-HT1A receptor binding or the decreased 5-HT2 receptor binding was observed in both the patients who had been medicated with neuroleptics at time of death and those who had not, at least 2 months prior to death. [1993] These data imply that chronic cannabinoid treatment may up-regulate 5- HT2A receptor activity while concurrently down-regulating 5-HT1A receptor activity, a finding similar to that sometimes observed in depression. [2006] We propose that the spectral data following the lower ipsapirone dose reflect a net decrease of neuronal activity at 5-HT2 receptors, mediated through stimulation of somatodendritic autoreceptors in the raphe nuclei (presynaptic) and/or through stimulation of postsynaptic 5-HT1A receptors colocalized with 5-HT2 receptors. [1996] Taken together, these results are in accordance with the hypothesis that 5-HT1A receptor activation exerts an inhibitory effect on activation of 5-HT2 receptors. [1999] Nefazodone's potent 5-HT2 antagonism in combination with 5-HT reuptake inhibition appears to enhance 5-HT1A-mediated neurotransmission. [1993] Tritiated (3H)-lysergic acid diethylamide (LSD) binding to 5-HT1A-D and 5-HT2 receptors and 3H-8-hydroxy-2-[di-N-propylamine]tetralin (8- OH-DPAT) binding to 5-HT1A receptors were used to quantify and map the distribution of these serotonin receptors between 4 and 60 postnatal days. [2004] Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. [2004] No expression of both 5-HT2A and 5-HT1D alpha receptors was detected in the caudate nucleus and in putamen where only a light labeling by means of the 5-HT1A receptor probe was detected. [1996] The rapid increase in serotonin (5-HT) synaptic levels by blockade of alpha2-heteroreceptors indirectly enhances 5-HT1A-mediated neurotransmission since 5-HT2 and 5-HT3 are blocked by mirtazapine. [1999] One compound (1g) demonstrated high affinity for 5-HT1A and D2 receptor binding sites and one compound (1d) proved to be a mixed 5- HT1A/5-HT2A ligand. [2000] Based on these findings, we conclude that NMDAR-dependent LTP is specifically inhibited by coactivation of 5-HT1A and 5-HT2 receptors with the increase in 5-HT levels in the rat visual cortex at the end of the critical period. [2006] Functional and radioligand binding studies in human isolated intrapulmonary arteries and veins have demonstrated a mixed population of 5-HT1B/1D and 5-HT2A receptors mediating vasoconstriction but no evidence of involvement of 5-HT1A, 5-HT3 [?] and 5-HT4 [?] receptors. [1999] Binding experiments at cloned human 5-HT1A, 5-HT1B, and 5-HT1D receptors show that these derivatives are potent and selective ligands for 5-HT1B/1D subtypes with increased binding selectivity versus the 5-HT1A receptor when compared to 1-naphthylpiperazine (1- NP). [1997] ATP pretreatment blocked the inhibitory effect produced by 5-HT 2C receptor activation on the 5-HT 1A, but not the 5-HT 1B, receptor response, suggesting that the 5-HT 1A receptor itself was the target for PLD/PKC action. [2003] These data suggest that the alterations in agonist-stimulated 5-HT1A receptor activation in depressed suicide victims are also manifest downstream from the associated G protein, affecting the activity of second messengers in two 5-HT1A receptor transduction pathways that may have implications for cell survival. [2003] The proposed neuroprotective mechanisms of repinotan are thought to be the result of neuronal hyperpolarization via the activation of G protein-coupled inwardly rectifying K+ channels upon binding to both pre- and post-synaptic 5-HT1A receptors. [2005] In addition, 5-HT7 receptor-mediated stimulation of adenylyl cyclase activity in this tissue appears to be augmented by a mechanism involving 5-HT1A receptor activation. [1999] Within the limitations that attend the use of pindolol as a 5-HT1A receptor antagonist, the data suggest that although 5-HT1A receptors may play a role in the tonic release of PRL, they are not involved in the release of PRL produced by d-FEN. [1995] To clarify the possible contribution of 5-HT1A receptor stimulation to the ability of L-5-HTP to stimulate cortisol and PRL secretion in man, the effect of pindolol, a beta adrenoceptor antagonist that is also a 5-HT1A partial agonist, on the L-5-HTP-induced increases in cortisol and PRL secretion, was examined in 12 normal male volunteers. [1994] With the exception of the hypoglossal nucleus, where 5-HT1A receptor binding increases while SERT binding remains stable, the medullary 5- HT markers analyzed in the study are essentially " in place " at birth. [2004] top Activation of 5-HT 1A receptor stimulated extracellular signal- regulated kinase (ERK)1/2, Akt and nuclear transcription factor- kappaB (NF-kappaB). [2005] Stimulation of cells with 5-HT 1A receptor agonist induced a rapid but transient ERK1/2 phosphorylation followed by increased phosphorylation of Akt. [2005] In contrast, activation of 5-HT1A receptors stimulated only a 2.8- fold maximal activation of ERK2 in transfected cells expressing receptors at 300 fmol/mg of membrane protein but did stimulate a 12- fold increase in activity in cells expressing receptors at 3,000 fmol/mg of membrane protein. [1999] Repinotan HCl (repinotan, BAYx3702), a highly selective 5-HT1A receptor agonist with a good record of safety was found to have pronounced neuroprotective effects in experimental models that mimic various aspects of brain injury. [2005] Whereas, the 5-HT1A receptor genotype did not show any significant effects on [11C]WAY 100635 binding, 5-HT1A receptor binding potential values were lower in all brain regions in subjects with 5-HTTLPR short (SS or SL) genotypes than those with long (LL) genotypes. [2005] We tested the hypothesis that 5-HT1A receptor agonists increase striatal dopamine release in man using PET scanning with the selective D2 receptor radioligand [11C]raclopride, which is sensitive to endogenous dopamine levels. [2005] The effect of 5-HT on ERK [?] activation appeared to be mediated through the activation of 5-HT1A receptors since similar results were obtained with R-+-8-hydroxy-DPAT, a selective 5-HT1A receptor agonist and WAY100635, a selective 5-HT1A receptor antagonist, reversed the 5- HT and the R-+-8-hydroxy-DPAT effects. [2004] The 5-HT1A receptor gene is repressed by NUDR/DEAF-1 in raphe cells at the C-, but not at the G-allele of the C(-1019)G polymorphism that is associated with major depression and suicide. [2004] The association with major depression, suicide, and panic disorder of a new functional 5-HT1A polymorphism at C(-1019)G that selectively blocks repression of the 5-HT1A autoreceptor by NUDR further suggests a causative role for altered regulation of this receptor in predisposition to mental illness. [2004] NUDR protein was colocalized with 5-HT1A receptors in serotonergic raphe cells, hippocampal and cortical neurons, and adult brain regions including raphe nuclei, indicating a role in regulating 5- HT1A autoreceptor expression. [2003] All mixed serotonin- and 5-HT1A-receptor agonists suppressed GH secretion in 10-day-old pups. [1996] However, in nonserotonergic cells that express 5-HT1A [?] receptors (septal SN48, neuroblastoma SKN-SH, and neuroblastoma/glioma NG108-15 cells), Deaf-1 [?] enhanced 5-HT1A [?] promoter activity at the C(- 1019)-allele but not the G-allele, whereas Hes5 repressed in all cell types. [2006] Limbic reductions of 5-HT1A receptor binding in human temporal lobe epilepsy. [2004] The 5-HT1A receptor gene is negatively regulated in neurons by repressors including REST/NRSF, Freud-1, NUDR/Deaf-1, and Hes5. [2004] These results suggest that IFN affects the low-affinity 5-HT1A receptors sites and may be involved in the development of IFN-induced psychiatric disturbances. [1999] Activation of 5-HT1A receptors expressed in NIH-3T3 cells induces focus formation and potentiates EGF [?] effect on DNA synthesis. [1992] The intrinsic activity of the compounds was evaluated by measuring their effect on VIP-stimulated cAMP production in GH4ZD10 cells stably transfected with the 5-HT1A receptor. [2000] Molecular dynamics (MD) simulations of ligand-receptor complexes were performed for each investigated analogue, docked twice into the central cavity of 5-HT1A/5-HT2A, each time in a different orientation. [2001] Previous studies with direct-acting serotonin (5-HT) agonists and antagonists have demonstrated that stimulation of 5-HT1A, 5-HT1C and 5-HT2 receptors may promote cortisol and prolactin (PRL) secretion in man. [1994] It is also possible that both 5-HT1A and 5-HT2/1C receptors stimulate PRL release, but 5-HT1A receptors may have a more prominent role in GH secretion. [1990] top Current evidence, based partly on the ability of selective serotonin receptor antagonists to prevent the increases in ACTH and corticosterone in rats in vivo, implicates 5-HT1A and 5-HT2/5-HT1C receptor subtypes in regulating CRF secretion. [1990] The coapplication of 5-HT1A and 5-HT2 receptor agonists inhibited the induction of NMDAR-dependent LTP in 5-HT-depleted slices. [2006] Previous reports based on studies with serotonin (5-HT) precursors or direct acting agonists have suggested that postsynaptic 5-HT1A and 5- HT2A/5-HT2C receptors may stimulate cortisol and prolactin (PRL) secretion in man. [1995] We found that 5-HT1B receptors couple better to activation of ERK2 and inhibition of adenylyl cyclase than do 5-HT1A receptors. [1999] After masking 5-HT1A receptors by 0.1 microM 8-OH-DPAT, the binding displaced by 0.1 microM 5-CT presumably represented 5-HT1D sites and the remaining binding 5-HT1E sites. [1994] HCR [?] expressed higher levels of 5-HT1B autoreceptor mRNA in the raphe nuclei relative to LCR, but similar levels of TPH, 5-HTT, and 5- HT1A mRNA in these areas. [2006] Application of 5-HT or DA in oocytes coexpressing 5-HT1A receptors and G-protein-activated inwardly rectifying potassium channels (GIRK1) induced inward currents with respective EC50 values of 4.2 nM and 11.2 microM. [2003] Compound (+)-12a demonstrated potent hSERT binding (Ki = 0.18 nM) in vitro and was more than 1000-fold less potent at hDAT, hNET, 5-HT1A [?], and 5-HT6. [2005] In fact, 5HT1A [?] and 5HT2 receptor agonists have been shown to prevent glutamate-induced neurotoxicity in primary cortical cell cultures and the 5-HT [?] precursor 5-hydroxytryptophan (5-HTP) improved locomotor function and survival of transgenic SOD1 G93A mice, an animal model of ALS. [2006] From Schild analysis, SB-649915 caused a concentration-dependent, rightward shift of 5-HT [?]-induced stimulation of basal [35S] GTPgammaS binding in cells expressing human recombinant 5-HT1A or 5- HT1B receptors to yield pA2 values of 9.0 and 7.9, respectively. [2006] Additionally, repeated cocaine exposure produces subsensitive 5-HT1A- mediated hormone responses, and supersensitive 5-HT2-mediated responses. [1994] Among 5-HT receptors, 5-HT1A receptors are related to some forms of myoclonus, although 5-HT2 receptors are also implicated. [1990] These data demonstrate that most antimigraine drugs display high affinity for the 5-HT1A and/or 5-HT2 receptor subtypes in human brain. [1988] In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5- HT2A antagonist ketanserin. [2005] Thus it is postulated that one mechanism, among others, through which exogenous thyroid hormones may exert their modulatory effects in affective illness is via an increase in serotonergic neurotransmission, specifically by reducing the sensitivity of 5-HT1A autoreceptors in the raphe area, and by increasing 5-HT2 receptor sensitivity. [2002] CONCLUSIONS: These data indicate that withdrawal from chronic cocaine renders specific subpopulations of postsynaptic 5-HT1A receptors subsensitive and 5-HT2A/2C receptors supersensitive. [1998] Moreover, SB-224289 antagonized the learning deficit produced by TFMPP (a 5-HT1A/1B/1D/2A/2C receptor agonist), GR 46611 (a 5- HT1A/1B/1D receptor agonist), mCPP (a 5-HT2A/2C/3/7 receptor agonist/antagonist) or GR 127935 (at low dose). [2001] Punctate sites of immunofluorescence were found on the surfaces of fibroblasts that expressed 5-HT1C and 5-HT2 receptors, but not on the surfaces of HeLa cells that expressed 5-HT1A receptors. [1991] Serotonin1A (5-HT1A) and serotonin2A (5-HT2A) receptors in the brain have been implicated in the pathophysiology of suicide. [1997] Human 5-HT1A sites can be distinguished from human 5-HT1B, 5-HT2, and 5-HT3 sites and from equivalent sites in rat and bovine cortex. [1985] top It is concluded that the anti-idiotypic antibodies generated with anti-5-HT serum recognize the 5-HT1B, 5-HT1C, and 5-HT2 receptor subtypes; however, neither 5-HT1A receptors nor 5-HT uptake sites appear to react with these antibodies. [1991] Two binding sites were detected in the presence of 1 microM pindolol (to block 5-HT1A and 5-HT1B receptors), and 100 nM mesulergine (to block 5-HT1C and 5-HT2 receptors). [1989] RU 24969, with high affinity for both 5-HT1A and 5-HT1B receptors, and 1-(2-methoxyphenyl)piperazine, a 5-HT1 compound, increased punished responding to a lesser extent, as did the 5-HT2 antagonists ketanserin and ritanserin. [1989] These approaches include combinations of SSRI activity with either NA reuptake inhibition or 5-HT1A-, 5-HT2-, or alpha 2-adrenergic receptor specificity, as well as targeting interactions with specific receptor subtypes (5-HT1A, 5-HT1A/5-HT2, 5-HT1B/D, alpha 2/5-HT2, D2/D3). [1998] Thus, studies of locomotor and investigatory responses can be used to demonstrate and differentiate the effects of direct agonists at 5- HT1A, 5-HT1B, and 5-HT2 receptors as well as indirect serotonin agonists. [1996] Further supporting the relevance of 5-HT1B receptors to the activating effects of serotonin-releasing agents, MDMA exhibits reciprocal cross-tolerance with the 5-HT1B agonist RU 24969, but not with either 5-HT1A or 5-HT2 agonists or amphetamine. [1996] In contrast, these sites showed low affinity for drugs with high affinity and/or selectivity for 5-HT1A (8-OH-DPAT, buspirone), 5-HT1B (21-009, RU 24969), 5-HT1C (mesulergine, mianserin) and 5-HT2 sites (ketanserin, cinanserin). [1988] Serotonin (0.5-100 microM) and the specific 5-HT2 receptor agonist, 1- (2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (10-100 microM) but not the 5-HT1A or 5-HT1B agonists, (+/-) 8-hydroxy-dipropylamino- tetralin (8-OH-DPAT) or 5-methoxy-3-3-(1,2,3,6-tetrahydro-4-pyridin) 1H-indole succinate (RU 24969) induced dose-dependent PKC translocations. [1990] We report on 5-HT1A, 5-HT1D, and 5-HT2 binding sites in 23 control subjects and 18 suicide victims subdivided according to the method of death and the previous existence of depressive symptoms. [1994] The rank order of potency of agonists as inhibitors of the [3H]5-HT overflow was 5-HT > sumatriptan (5-HT1D/1B) > 8-hydroxy-2-(di-n- propylamino)tetralin (5-HT1A/1D) >> 1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane HCl (5-HT2/1C). [1993] In contrast to published reports which show that cocaine exposure produces supersensitive 5-HT2A and/or 5-HT2C receptor-mediated responses, the present data suggest that repeated cocaine exposure produces subsensitivity to at least some postsynaptic 5-HT1A receptors. [1994] The modest 5-HT2A antagonism and 5-HT2C partial agonism, along with reported D2 and 5-HT1A partial agonism, may allow aripiprazole to stabilize the disturbed dopamine-serotonin interplay in schizophrenia with a moderate yet adequate pharmacological intervention. [2006] A conclusive identification of the 5-HT receptor subtypes that are involved in this different action cannot be identified at present, but it should be taken into account that risperidone differs from clozapine, showing higher affinity for 5-HT2A than 5-HT2C receptors and lacking the marked affinity of clozapine to 5-HT1A receptors. [2001] One hundred and twenty-four subjects affected by bipolar (n=102) and major depressive (n=22) disorder were followed prospectively for an average of 52 months and were typed for 5-HT2A (T102C: n=111, HTP: n=104), 5-HT2C (n=110) and 5-HT1A (n=61) variants. [2000] METHODS: We studied the genetic association between alcoholism and alleles of the HTR1A, HTR2A, and HTR2C genes. [2000] Data set containing 1135 dopamine antagonists (D2, D3, and D4), 1251 serotonin antagonists (5-HT1A, 5-HT2A, and 5-HT2C), and 386 serotonin- dopamine dual antagonists was collected from the MDDR database. [2006] Assuming that genes regulating the serotonin system are involved in the pathogenesis of panic disorder, the authors searched for a genetic association of panic disorder with the serotonin 1A (HTR1A), 2A (HTR2A), and 2C (HTR2C) receptor genes. [2003] ORG 5222 was the most potent drug at dopamine D2 and 5-HT2c receptors, while ziprasidone was the most potent compound at three serotonergic receptors (5-HT1A, 5-HT1D, and 5-HT2A). [2000] The four stereoisomers of mesoridazine were synthesized and evaluated in D2, 5-HT1A, 5-HT2A, 5-HT2C, D1, and D3 receptor binding and functional assays. [2004] In other models, 5-HT1A and 5-HT2A/5-HT2C agonists exhibit antiemetic properties. [1999] top 4. 5-HT (1 microM)-mediated increases in [Ca2+]i were insensitive to the 5-HT receptor antagonist, ritanserin (5-HT2; 100 nM), ketanserin (5-HT2; 100 nM), LY-278,584 (5-HT3; 1 microM) and WAY 100635 (5-HT1A; 1 microM). [1995] Although chronic administration of 5-HT1A drugs appears necessary for clinical anxiolytic and antidepressant activity, the most noteworthy neuropharmacological effects in animals seem to occur in 5-HT2 and, perhaps, 5-HT3 receptors which are downregulated. [1993] Future studies of 5-HT1A receptor-effector complex function in conjunction with assessment of the responsivity of other subtypes (e.g. 5-HT2, 5-HT3) should promote the evaluation of 5-HT system integrity in anxiety disorders and its involvement in anxiolytic drug effects. [1992] Anxiolytic-like effect of a serotonergic ligand with high affinity for 5-HT1A [?], 5-HT2A and 5-HT3 [?] receptors. [2005] S-(-)-2-[[4-(napht-1-yl)piperazin-1-yl]methyl]-1,4- dioxoperhydropyrrolo[1,2-alpha]-pyrazine (CSP-2503) is a serotonin (5- HT [?]) receptor ligand with selectivity and high affinity for 5-HT1A [?], 5-HT2A and 5-HT3 [?] receptors. [2005] Antagonists with selective affinity at 5-HT1A/1B (propranolol), 5- HT1C (mesulergine), 5-HT2 (ketanserin, mianserin) and 5-HT3 (MDL 72222) sites were inactive to block the 5-HT-induced contraction. [1993] At variance with 5-HT1A and 5-HT3 [?], the binding at the 5-HT2A receptors is strongly endothermic and entropy-driven. [1995] A variety of serotonergic agents are now in preclinical and clinical development as anxiolytics, including 5-HT1A partial agonists, 5-HT2 antagonists, and 5-HT3 antagonists. [1990] The potentiating action of MKC-242 was antagonized by WAY100635, a selective 5-HT1A receptor blocker, but not by ritanserin, a 5-HT2 [?]/5-HT7 receptor blocker, indicating that MKC-242 is activating 5- HT1A receptors. [1998] To this end, pulmonary ventilation (V(E)) of rats was measured before and after intra-AVPO microinjection of methysergide (a 5-HT1 and 5- HT2 receptor antagonist), WAY-100635 (a 5-HT1A receptor antagonist) and SB-269970 (a 5-HT7 receptor antagonist), followed by 60 min of hypoxia exposure (7% O2). [2006] PRL secretion due to 5-HT formed from exogenous L-5-HTP may require the availability of both intact 5-HT1A and 5-HT2/5-HT1C receptors, since blockade of either receptor type inhibited the PRL response to L-5-HTP. [1994] Activation of alpha-1 adrenergic receptors, but not 5-HT2A receptors, had effects on 5-HT1A receptor responsiveness similar to those seen with PMA pretreatment. [1996] Taken together, the results neither explain the suggested greater efficacy in producing anxiolytic effects of compounds with putative mixed 5-HT1A agonist and 5-HT2A/2C antagonist properties, nor confirm a proposed interaction between alpha1 adrenoreceptors and 5-HT1A agonists in preclinical tests of anxiolytic activity. [1996] The tested compounds showed high affinity for the 5-HT1A receptor (Ki = 1.3-79.2 nM) and moderate to low affinity for the 5-HT2A (Ki = 51.7- 1405 nM) and alpha1 receptors (Ki = 19.7-382.3 nM). [2006] RBI-257 had much lower affinity at D1 and D5 dopamine receptors in transfected cells, as well as dopamine D1-like receptors, alpha1, alpha2 or beta(1,2) adrenoceptors, sigma(1,2) receptors and 5-HT1A or 5-HT2A receptors, and transporters for dopamine, norepinephrine or serotonin in rat forebrain tissue. [1997] New 4-aryl-2H-pyrido[1,2-c]pyrimidine-1,3-dione derivatives of arylpiperazine (6-18) were prepared and evaluated in vitro for their affinity for 5-HT1A, 5-HT2A, and alpha1 receptors. [2006] The use of functional imaging technique, such as PET or SPET evaluation of brain Serotonin transporters and 5-HT1A and 5-HT2A receptors allow for direct in vivo estimation of serotonergic function. [2006] Aripiprazole, the most recently introduced atypical APD, and a D2 receptor partial agonist, may also owe some of its atypical properties to its net effect of weak D2 antagonism, 5-HT2A antagonism and 5-HT1A agonism [Eur. J. Pharmacol. 441 (2002) 137]. [2003] Three dimensional models of the 5-HT1A and 5-HT2 receptor and of the dopamine D2 receptor were constructed from the amino acid sequences. [1991] 8-OH-DPAT (1 microM) and renzapride (3 microM) were without effect on forskolin-stimulated cyclic AMP production and ketanserin (0.3 microM) did not antagonize the inhibition produced by 5-HT, thus excluding the involvement of 5-HT1A, 5-HT4, and 5-HT2 receptors. [1996] top Following on from the suggestion that nefazodone, a specific serotonin reuptake inhibitor and antagonist of 5-HT2, improves 5-HT1A- mediated transmission, we used a pindolol and nefazodone combination treatment for major depressive disorder. [1997] Synthesis of new hexahydro- and octahydropyrido[1,2-c]pyrimidine derivatives with an arylpiperazine moiety as ligands for 5-HT1A and 5- HT2A receptors. Part 4. [2006] Synthesis of new hexahydro- and octahydropyrido[1,2-c]pyrimidine derivatives with an arylpiperazine moiety as ligands for 5-HT1A and 5- HT2A receptors. Part III. [2004] A 5-HT1A receptor agonist, 8-hydroxy-dipropylaminotetralin (DPAT, 10(- 6) to 10(-4) M) stimulated the formation of platelet cyclooxygenase (CO) products, whereas (+/-)1-(2,5-dimethoxy-4-iodo phenyl)-amino propane hydrochloride (DOI, 10(-6) to 10(-4) M), a 5-HT2 receptor agonist, had no significant effect on CO product formation. [1990] Animals received 12 d administration of the potent cannabinoid receptor agonist HU-210 (100 microg/kg), following which they were monitored on their behavioural, physiological and hormonal responses to a single challenge of a 5-HT1A and 5-HT2A receptor agonist, 8-OH- DPAT (0.3 mg/kg) and DOI (1 mg/kg) respectively. [2006] Atypical antipsychotics are also a heterogeneous group of agents that have complex pharmacologic entities, acting upon multiple dopamine receptors (D2, D1, D3, and D4) and multiple serotonin receptors (5- HT2A, 5-HT2C, 5-HT1A, and 5-HT1D, among others). [2004] Correlation analysis between the potencies of different agonists and antagonists at the cyclase in these cells and their reported relative potencies for different serotonin receptor subtypes showed no correlation with the 5-HT1A, 5HT1B, 5HT1D, 5-HT2, and 5-HT3 receptors. [1990] Eleven subtypes of central 5-HT receptor have so far been postulated, four of which have been cloned (5-HT1A, 5-HT1C, 5-HT1D and 5-HT2) and a fifth (the 5-HT3 receptor) purified. [1992] To examine further the role of 5-HT1A and 5-HT2A/5-HT2C receptors in prolactin and cortisol secretion in healthy men, the effects of meta- chlorophenylpiperazine (mCPP), a potent 5-HT receptor agonist, on the above hormones were studied in eight healthy men with and without pindolol pretreatment. [1995] We have re-screened the genes for the 5-HT1A, 5-HT2A, 5-HT2C, and 5- HT7 serotonin receptors for genetic variants in a large African- American and Caucasian-American population sample. [2004] Single-nucleotide polymorphisms (SNPs) in five serotonin receptor genes (HTR1A, HTR1B, HTR2A, HTR2C and HTR6) and the 5-HT transporter- linked polymorphic region (5-HTTLPR) were genotyped. [2006] Stimulation of 5-HT1A, 5-HT1B, 5-HT2A/2C, 5-HT3 and 5-HT4 receptors or 5-HT uptake inhibition: short- and long-term memory. [2007] They also indicate in the human brainstem a prominence of 5-HT1A sites and paucity of 5-HT1D, 5-HT1E/F, and 5-HT2A sites, which has implications for brainstem-mediated myoclonus and response to serotonergic drugs. [1996] Emerging evidence also indicates that 5-HT1A and 5-HT4 receptor agonists, as well as, 5-HT1A antagonists, 5-HT2 antagonists, 5-HT3 antagonists and 5-HT uptake inhibitors may have therapeutic utility in the treatment of Alzheimer's disease and amnesia. [1998] The [3H]8-OH-DPAT bindings to the prefrontal cortex and hippocampus were potently inhibited by serotonin (IC50 = 6.3 x 10(-9) M) and 5- HT1A agonists (IC50 = 5.0 x 10(-9) - 2.3 x 10(-7) M), while other neurotransmitters, 5-HT2 and 5-HT3 related compounds did not inhibit the binding (IC50 greater than 10(-5) M). [1991] Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5- HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. [2007] At least seven receptor subtypes (5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5- HT2, 5-HT3, 5-HT4) have been identified in brain. [1991] The approaches for mathematical modeling of signaling pathways activated by 5-HT receptors are described briefly in the context of ongoing work on detailed biochemical models of 5-HT2A, and combined 5- HT2A/5-HT1A, receptor-mediated activation of the MAPK [?] 1,2 pathway. [2005] RT-PCR products corresponding to the human 5-HT2A, 5-HT1B and 5-HT1F receptors were expressed in high levels, mRNAs coding for 5-HT7, 5- HT1A and 5-HT1D receptors were only weakly expressed. [1999] There are several significant correlations between affinities for the 5-HT1A, 5-HT2A, histamine1, alpha-1 [?] and alpha-2 receptors. [1997] top The Ki values for eight of the antidepressants and three metabolites were also determined for the rat 5-HT1A, 5-HT2A and muscarinic cholinergic receptors, the guinea pig histamine1 receptor and the human alpha-1 [?] and alpha-2 receptors. [1997] The 5-HT1 sites have been further divided into 5-HT1A, 5-HT1B, 5- HT1C, 5-HT1D and 5-HT1E sites. [1990] To investigate the non-5-HT1D component of the binding, 100 nM 5-CT (to block 5-HT1A, 5-HT1B, and 5-HT1D receptors) was coincubated with [3H]5-HT, membranes, and mesulergine. [1989] Pharmacological data from binding and cyclic AMP production studies indicate that this receptor does not have characteristics of a 5- HT1A, 5-HT1C or 5-HT1D receptor, but is similar to 5-HT1B receptors found in rodent tissues. [1989] The affinity of clozapine for 5-HT2A, 5-HT2C, 5-HT6, 5-HT7, and 5- HT1A receptors has been suggested to contribute to various aspects of its complex clinical actions. [2001] This compound showed a multi-receptor profile with affinities similar to those of clozapine for serotonin (5-HT2A, 5-HT1A, and 5-HT2C), dopamine (D1, D2, D3 and D4), alpha-adrenergic (alpha1, alpha2), muscarinic (M1, M2) and histamine H1 receptors. [2006] Expression of seven serotonin or 5-hydroxytryptamine (5-HT) receptors (5-HT1D alpha, 5-HT1E, 5-HT2, 5-HT1A, 5-HT1C, 5-HT1D beta, and 5-HT6) was investigated in human normal fetal astrocytes and eight glioma cell lines by reverse transcription and polymerase chain reaction (RT- PCR). [1996] Interaction of 5-HT1B/D ligands with recombinant h 5-HT1A receptors: intrinsic activity and modulation by G-protein activation state. [1998] In the present study, the intrinsic activity of a series of 5-HT1B/D ligands was investigated at human 5-HT1A (h 5-HT1A) receptors by measuring G-protein activation in recombinant C6-glial and HeLa membranes, using agonist-stimulated [35S]GTPgammaS binding. [1998] The present study reports on G-protein activation by recombinant 5-HT receptors and by native 5-HT1A and 5-HT1B receptors in guinea-pig and rat brain using agonist-stimulated [35S]GTPgammaS binding responses mediated by a new 5-HT ligand, a dimer of sumatriptan. [1999] Multiple 5-hydroxytryptamine (5-HT) receptors have been identified (5- HT1A/1B/1D/1E/1F, 5-HT2A/2B/2C, 5-HT3A/3B, 5-HT4A/4B, 5-HT5A/5B, 5- HT6 and 5-HT7A/7B/7C/7D) and extensive evidence suggests that 5-HT receptors have a role in learning and memory. [1998] The receptors on which GLC756 binds (D1, D2, D4, alpha-1, alpha-2, 5- HT1A, 5-HT2C, 5-HT1D, 5-HT2 A, beta-1, and beta-2) were suggested to play a role. [2006] The allele and genotype frequencies of polymorphisms at the genes for serotonin receptors HTR1A, HTR1Dalpha, HTR1Dbeta, HTR2A, HTR2C, HTR7, tryptophan hydroxylase (TPH), and the serotonin transporter (hSERT) were compared in the two groups of subjects. [1999] Because 5-HT dysregulation is associated with several common psychiatric disorders, the potential for epistasis among genetic variants in the 5-HT transporter (SERT), 5-HT1B terminal autoreceptor and the 5-HT1A somatodendritic autoreceptor should be examined. [2005] Parameters representing extracellular 5-HT clearance rates (SERT), 5- HT release levels (5-HT1B) and inhibitory thresholds (the amount of extracellular 5-HT above which cell firing is inhibited, an indication of 5-HT1A autoreceptor sensitivity) were varied to simulate genetic deletion (i.e. knockout) of each component singly, and in combination. [2005] With the use of reverse-transcription polymerase chain reaction, normal rat aortic cusps were shown to express mRNA for serotonin receptors 5-HT1A [?], 5-HT2A, and 5-HT2B and the serotonin transporter 5-HTT. [2005] These findings demonstrate that although both 5-HT1A and 5-HT1B receptors have been shown to couple to G proteins of the Gi class, they exhibit differences in coupling to ERK2 and adenylyl cyclase. [1999] Different displacers were used to mask radioligand binding to 5-HT1A, 5-HT1B/1D and 5-HT2C receptors, in an attempt to visualize other receptor populations, which presumably would correspond to 5-HT1E and 5-HT1F sites. [1996] We evaluated the suitability of fluorocarazolol for in vivo studies of cerebral beta-adrenoceptors because (S)-1'-[18F]fluorocarazolol has a higher affinity to beta-adrenoceptors than to serotonergic receptors (pKi beta 1 9.4, beta 2 10.0, 5HT1A 7.4, 5HT1B 8.1) and rapidly crosses the blood-brain barrier. [1997] To foster uniform definitions of locations within these nuclei, we have quantitatively mapped gene expression in DRN and MRN for tryptophan hydroxylase-2 [?] (Tph2 [?]), the serotonin transporter, as well as 5-HT1A and 5-HT1B receptors. [2006] top Likewise, the stimulation or blockade of presynaptic 5-HT1A, 5-HT1B, 5-HT(2A/2C) and 5-HT3 receptors, postsynaptic 5-HT(2B/2C) and 5-HT4 receptors and 5-HT uptake/transporter sites modulate these processes. [1999] 5. The blockade of postsynaptic 5-HT1A, 5-HT1B, 5-HT3 or 5-HT4 receptors and 5-HT inhibition of synthesis and its depletion did no alter learning by themselves. [1997] Both E and DHE are 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT1F receptor agonists. [1997] Using a high-throughput single-nucleotide polymorphism (SNP) genotyping platform and capillary electrophoresis, we genotyped patients at 110 SNPs and four repeat polymorphisms located in seven candidate genes (HTR1A, HTR2A, HTR2C, MAOA, SLC6A4, TPH1, and TPH2). [2004] The G protein coupling behavior of four human 5-hydroxytryptamine receptor subtypes (5-HT1A, 5-HT1B, 5-HT1D, and 5-HT1E) has been studied in membranes from Sf9 cells expressing the individual receptors. [1997] Genes regulating the synthesis (TPH), storage (VMAT2), membrane uptake (HTT [?]), and metabolism (MAOA) of 5-HT, as well as a number of 5-HT receptors (HTR1A, HTR1B, HTR2A, HTR2C, and HTR5A), have been studied and this initial research is reviewed here. [2000] Lorcaserin was also highly selective for human 5-HT2C over other human 5-HT receptors (5-HT1A, 5-HT1B, 5-HT3, 5-HT4C, 5-HT5A, 5-HT6, and 5-HT7), in addition to a panel of 67 other GPCRs and ion channels. [2008] Thus, mCPP-induced prolactin secretion appears to require the availability of both 5-HT2C and 5-HT1A receptor activation, since blockade of either of these receptors may diminish the mCPP-induced prolactin response. [1995] In conclusion, in transfected NIH-3T3 cells, transforming and mitogenic effects of 5-HT1A agonists involve a pertussis toxin- sensitive G protein [?] but do not seem to be linked to adenylyl cyclase inhibition. [1992] In conclusion, G-protein activation by 5-HT1A receptors can be measured in human and monkey brain sections. [1999] In the present study, we investigated whether similar receptor/G- protein alterations would occur at the 5-HT1A receptor in the same brain area. [1996] In these two membrane preparations, the density of h 5-HT1A receptors (i.e., 246 to 320 fmol mg(-1) protein) and of their G-proteins, and the receptor: G-protein density ratio (0.08 to 0.18) appeared to be similar. [1998] Activation of 5-HT7 receptors was thought to be responsible for the shift, despite the clear preference of 8-OH-DPAT for 5-HT1A sites in terms of receptor binding affinity. [2004] By itself, 8-OH-DPAT produced a concentration-dependent phase advance that was sensitive to co-application with 5-HT7 antagonists (ritanserin, mesulergine, SB-269970), but not to 5-HT1A antagonists (WAY-100,635, UH-301). [2004] By aiding in the identification of the 5-HT receptor subtype responsible for the observed phase shifts and cAMP changes, 8-OH-DPAT represents an important pharmacological tool for 5-HT7 receptor activation, essentially broadening its role as the prototypical 5- HT1A agonist to one combining these two receptor activities. [2004] WAY-100635 and NAN-190, 5-HT1A receptor antagonists, reversed the impairment of spatial memory induced by systemic injection of 8-OH- DPAT (1 mg/kg, i.p.). On the other hand, the alpha1-adrenoceptor antagonist prazosin and a selective 5-HT7 receptor antagonist SB269970 had no effect on 8-OH-DPAT-induced impairment of spatial memory. [2006] The specific binding of [3H]8-OH-DPAT to serotonin7 (5-HT7) and serotonin1A (5-HT1A) receptors was investigated by competitive inhibition with ritanserin and pindolol, respectively. [1999] The evidence suggests that the PRL response to LTP is mediated by 5- HT1 receptors, perhaps the 5-HT1A subtype, though further studies are needed to confirm this effect. [1990] We studied the effect of the 5-HT1A receptor antagonist, pindolol, on the prolactin (PRL) response to the 5-HT releasing agent, d- fenfluramine (d-FEN), in ten healthy male volunteers. [1995] Pindolol alone decreased basal plasma PRL levels and increased basal plasma cortisol levels, possibly due to 5-HT1A antagonist and agonists effects, respectively. [1994] top These data, coupled with observations from other studies, suggest that the L-5-HTP-induced increase in PRL but not cortisol secretion requires 5-HT1A receptor activation. [1994] In human cortex and hippocampus area, [3H]5-HT (5 nM) labels 5-HT1A, 5-HT1D and 5-HT1E sites. [1994] The highest densities of 5-HT1E sites have been measured in subiculum, where 5-HT1A, 5-HT1D and 5-HT1E binding sites were equally represented and in entorhinal cortex where 5-HT1E sites represented the major binding in layer III. [1994] Augmented PRL response to mCPP could derive from 5-HT1A receptor hypersensitivity, perhaps as as a consequence of anxiety due to pain expectation. [1998] The subjects were also typed for 5HT1A and 5HT2C variants using polymerase chain reaction techniques. [2000] In parallel, the suppressed social interaction elicited by intra-DRN administration of NMB was attenuated by a systemically administered 5- HT2C (but not 5-HT1A) receptor antagonist. [2006] Using quantitative in situ hybridization, we measured messenger RNA (mRNA) levels of tryptophan hydroxylase (TPH), 5-HT transporter (5- HTT), 5-HT1A and 5-HT1B autoreceptors, dopamine receptor-D2 (DR-D2) autoreceptors and postsynaptic receptors, and dopamine receptor-D1 (DR-D1) postsynaptic receptors, in discrete brain regions of HCR [?] and LCR. [2006] In this regard, it is probable that selective drugs with agonists, neutral antagonist, agonists or inverse agonist properties for 5- HT1A, 5-HT(1B/1D), 5-HT(2A/2B/2C), 5-HT4 and 5-HT7 receptors could constitute a new therapeutic opportunity for learning and memory alterations. [1999] Across all three regimens, Dex administration evoked upregulation of cerebrocortical 5HT1A and 5HT2 receptors and the presynaptic 5HT transporter, greatest for 5HT1A receptors. [2006] Pharmacological and clinical studies have shown that the 5-HT transporter (5-HTT) and the 5-HT1A receptor appear to be candidate loci for the aetiology of alcohol dependence. [1999] Whereas there was no significant change in the number of substance P and calcitonin gene-related peptide-positive nerve fibres between the involved and non-involved skin, there was an increase in the epidermal fraction of 5-hydroxtrytamine 1A (5-HT1A) receptor and serotonin transporter protein (SERT [?]) immunoreactivity in the involved skin. [2008] DRN 5-HTT sites, 5-HTT mRNA and 5-HT1A binding concentration showed no change between suicides and controls; suicides had 54% fewer DRN neurons expressing 5-HTT mRNA compared with controls but expression per neuron was greater in suicides. [2006] In the PET group, we also studied the influence of a common variable number tandem repeat polymorphism [short (S) and long (L) alleles] of the 5-HT transporter (5-HTT) gene on 5-HT1A receptor density. [2005] A test series of 32 phenylpiperazines III with affinity for 5-HT1A and alpha1 receptors was subjected to QSAR analysis using artificial neural networks (ANNs), in order to get insight into the structural requirements that are responsible for 5-HT1A/alpha1 selectivity. [1999] Compounds 8 and 10 showed the highest 5-HT1A receptor affinity (Ki = 1.3 and 2.2 nM, respectively) and were 37- and 35.9-fold, respectively, more selective in relation to alpha1 adrenoreceptors. [2006] Polymorphisms in the 5-HT6 (HTR6), 5-HT1A (HTR1A) and 5-HT7 (HTR7 [?]) receptor genes were genotyped. [2001] This study examined the hypothesis that genetic variation in 5-HT1A, 5-HT6, and 5-HT7 receptor genes is involved in the variability observed in response to clozapine. [2001] Treatment with CP's alone indicated that agonistic effects on beta-2 adrenoceptors and antagonistic effects on alpha-2, 5-HT1A and 5-HT1D receptors resulted in statistically significant decreased TNF-alpha levels in comparison to the LPS-control group. [2006] Attenuated 5-HT1A receptor signaling in brains of suicide victims: involvement of adenylyl cyclase, phosphatidylinositol 3-kinase, Akt and mitogen-activated protein kinase. [2003] Regional brain activation on visual presentation of emotional facial stimuli was investigated in 20 patients with panic disorder by means of fMRI at 3 T. All patients were genotyped for the functional - 1019C/G 5-HT1A and 5-HTTLPR polymorphisms. [2006] top In this study, the influence of two genetic factors on 5-HT1A receptor expression in the living human brain was assessed using the 5-HT1A-selective positron emission tomography (PET) ligand [11C]WAY 100635. [2005] In CA3-CA4 fields, 5-HT1A receptors were less densely present, 5-HT1D sites were predominant and 5-HT1E sites represented a significant fraction (27%). [1994] 2) In the receptor binding assays, cephaeline and emetine had a distinct affinity to 5-HT4 receptor, but no or weak affinity to 5- HT1A, 5-HT3 [?], nicotine, M3, beta1, NK1 [?], and D2 receptors. [2002] Examination of the ACTH response to 5-HT1A agonists may represent a valuable approach to determine deficits in 5-HT function in human cocaine abusers. [1994] Cocaine-induced deficits in the ACTH response to 5-HT releasers may reflect 5-HT1A receptor subsensitivity, but presynaptic deficits cannot be excluded. [1994] There is also evidence that 5-HT1A receptors can increase ACTH secretion. [1990] This suggests that in humans as in animals both the 5-HT1A and 5HT2/1C receptors can facilitate ACTH release, though the significance of this dual control is not understood. [1990] We performed 5-HTT and 5-HT1A binding, 5-HTT mRNA in situ and tryptophan hydroxylase (TPH) immunoautoradiography on depressed suicides and controls brainstem sections. [2006] The nonselective beta-adrenergic and selective 5-HT1A/1B receptor antagonist (+/-)pindolol was without effect on basal HPA activity, but completely antagonized the IPS-induced plasma ACTH and cortisol responses. [1990] The impaired hypothermic and ACTH/cortisol responses following 5-HT1A receptor activation reflects subsensitivity of both the pre- and post- synaptic 5-HT1A receptor-effector system, thus supporting the hypothesis that a 5-HT1A receptor-related serotonergic dysfunction may be linked to the pathophysiology of PD. [1992] Activation of central pre- and postsynaptic 5-HT1A receptors which are linked to the Gi-AC complex, induces hypothermia and ACTH/cortisol release in rodents and humans. [1991] EF-7412 acts an antagonist in vivo in pre- and postsynaptic 5-HT1A receptor sites and as an antagonist in dopamine D2 receptor. [1999] Anti-OPRM1 antibodies, anti-HTR1A antibodies, and anti-DRD2 antibodies were found in 15.2, 1.7, and 5.0% of patients with CFS, respectively. [2003] 5-HT activates ERK [?] MAP kinase in cultured-human peripheral blood mononuclear cells via 5-HT1A receptors. [2004] To elucidate these issues, we immunohistochemically examined vesicle monoamine transporter 2 (VMAT2 [?]), serotonin receptor type 1a (5HT1a), and serotonin transporter (5HTT [?]) in the hippocampal region of reserpine-treated rats, an animal model of depression. [2006] Our results indicate that 5-HT activates ERK [?], but not p38 [?], MAP kinase of human PBMC via a 5-HT1A receptor. [2004] In situ hybridization and quantitative image analysis was used to measure mRNAs coding for SERT (serotonin transporter), 5HT1A autoreceptor, MAO-A and MAO-B (monoamine oxidases) at six levels of the dorsal raphe nucleus (DRN). [2005] Thus, all serotonin-related mRNAs examined in the dorsal raphe to date were lower (SERT, MAO-A) or exhibited a lower trend (5HT1A, MAO- in the stress sensitive animals, which probably reflects the lower number of serotonin neurons present. [2005] Less 5-HT1A feedback inhibition and increased TPH could be compensatory changes in response to serotonin hypofunction. [2006] The activation of ERK [?] and Akt downstream of 5-HT 1A receptor was sensitive to inhibitors of Ras, Raf and phosphatidylinositol 3-kinase (PI3K [?]). [2005] top These findings suggest a role for 5-HT 1A receptor signaling in the Ras/Raf-dependent regulation of multiple intracellular signaling pathways that include ERK [?] and PI3K [?]/Akt. [2005] Thus, the intrinsic activity of Deaf-1 [?] at the 5-HT1A [?] promoter is opposite in presynaptic versus postsynaptic neuronal cells and requires deacetylation. [2006] Stable expression of NUDR in raphe cells reduced levels of endogenous 5-HT1A protein and binding. [2003] Our data indicate that NUDR is a repressor of the 5-HT1A receptor in raphe cells the function of which is abrogated by a promoter polymorphism. [2003] This is significant as the 1B and 1D receptor subfamilies are the target of the anti-migraine drug sumatriptan, and these receptors regulate cardiac function and movement; (ii) 5-HT 1A, 5-HT 1E and 5- HT 1F are not expressed in interstitial cells isolated from the valves. [2000] In support of the importance of 5-HT 1A receptor signaling for cell survival, inhibition of NF-kappaB facilitated caspase 3 activation and cleavage of poly (ADP-ribose) polymerase, while treatment of cells with agonist inhibited caspase 3, DNA fragmentation and cell death. [2005] Furthermore, microinjection of midazolam, of the NMDA receptor antagonist AP-7, or of the 5-HT1A/1B receptor blocker propranolol increased the exploration of the open arms of the elevated plus-maze, having therefore an anxiolytic effect. [1993] Recently, modulation of glucocorticoid receptor (GR) and serotonin receptor 1A (5-HTR1A) were implicated in mechanism(s) leading to depression. [2005] By contrast, muscarinic M1 and M2, 5-HT1A, benzodiazepine (including zolpidem-insensitive binding), NMDA [?] (MK801), and AMPA/QUIS receptors were higher in CA1 and/or subiculum. [1993] Experimental lesions using the retrogradely transported toxin, volkensin, have been used in conjunction with autoradiography to investigate the cellular localization of 5-HT1A, muscarinic M1 and nicotinic receptors. [1996] Selective destruction of layer V corticostriatal neurones was accompanied by loss of binding in the cortex to 5-HT1A and muscarinic M1 receptors, and an upregulation of [3H] nicotine binding contralateral to the pyramidal cell loss. [1996] Of these, only PI3K [?]/Akt and NF-kappaB activation were required for 5-HT 1A receptor-dependent cell survival, implying that the relative distribution of signals between competing transduction pathways determines the functional outcome of 5-HT 1A receptor activation. [2005] In particular, phenotypic changes in mice bearing inactivation mutations of 5-HT1A [?] and 5-HT1B receptors, 5-HT [?] transporter, 5- HT [?] neuron-specific transcription factor Pet1 [?], monoamine oxidase A and genes related to 5-HT [?] signalling will be discussed and major findings highlighted. [2005] Finally, ethanol did not block the reduction in responsiveness of the 5-HT 1A receptor system produced by activation of PKC with phorbol ester treatment, suggesting that PKC activation lies downstream of PLD. [2003] Taken together, these data suggest that activation of P 2Y receptors can reduce responsiveness of the 5-HT 1A receptor system via a PLD/PKC-dependent mechanism that is highly dependent upon the temporal pattern of receptor activation. [2003] In the hippocampus, 5-HT1A receptor mRNA was present in all fields, especially CA1. [1995] In the hippocampus, both alpha 2A- and non-alpha 2A- (alpha 2B- and alpha 2C-) adrenoceptors were labelled in the dentate gyrus and the CA1 field, together with 5-HT1A receptors. [1996] The three above mentioned ligands were tested on HeLa cells (cell line HA6) expressing recombinant human 5-HT1A receptors for their effects on forskolin-stimulated cAMP accumulation in intact cells. [1998] We examined the cell-specific activity of identified transcription factors, human nuclear deformed epidermal autoregulatory factor-1 (DEAF-1)-related (NUDR)/Deaf-1 and Hes5, at the 5-HT1A [?] C(-1019) site. [2006] Consistent with the linkage evidence, LHPP associations depended on HTR1A genotype. [2008] top Counteracting the 5-HT1A receptor with the 5-HT1A agonist 8-OH-DPAT could not prevent the TNF-alpha decreasing effect of GLC756. [2006] METHODS: In the present study, an analysis of interactions between the functional serotonin receptor 1A polymorphism, the norepinephrine transporter variants and the other respective polymorphisms of the above-mentioned genes is reported. [2006] A human neuroreceptor clone (G21), which was isolated by cross- hybridization with the human clone for the beta 2-adrenergic receptor, has recently been shown to encode the gene for the 5HT1A receptor (HTR1A) subtype. [1991] We have previously described a genomic clone, G-21, isolated by cross- hybridization at reduced stringency with a full length beta 2- adrenergic receptor probe. [1988] We have applied this method to explore the detergent resistance of an important G-protein coupled receptor, the serotonin1A (5-HT1A) receptor. [2004] Retrogradely labeled 5-HT neurons were found within the dorsal, median, and caudal linear raphe nuclei and are suspected to inhibit AVP-facilitated offensive aggression by an activation of 5-HT1A receptors in the AH. [1999] Patients were genotyped for HTR1A gene and, in addition, for two polymorphisms at the CYP2C19 gene, which together account for the 87% of the Caucasian poor metabolizer phenotype. [2005] Activation of D3 and/or 5-HT1A receptors may thus contribute to its potential antidepressant properties. [1999] RESULTS: A nominally significant (P=0.04) interaction between the serotonin receptor 1A and the catechol-O-methyltransferase polymorphisms was observed. [2006] 4. Using a metabolic pathway approach, it can be shown that the best current candidate gene locus for a subtype of schizophrenia located on chromosome 5q11-13 (HGML10 # SCZD1 and OMIM #181510) is in the serotonergic pathway, i.e. a receptor for 5-hydroxytryptamine (subtype 1A; HGML10 #HTR1A) which also maps in the same chromosomal region. [1991] Functional characterization of the novel antipsychotic iloperidone at human D2, D3, alpha 2C, 5-HT6, and 5-HT1A receptors. [2003] Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression. [2008] Our results show the involvement of specific 5-HT1A [?] receptor- dependent cellular events in acetaminophen-produced antinociception and consequently indicate that inhibition of cyclooxygenase activities is not the exclusive mechanism involved. [2007] Indeed, down-regulation of sst3R mRNA depends on acetaminophen- elicited, 5-HT1A [?] receptor-dependent increase in neuronal extracellular signal-regulated kinase 1 [?]/2 (ERK1 [?]/2) activities that mediate antinociception. [2007] Furthermore, we propose that the mechanisms of 5-HT1A [?] receptor- elicited antinociception and the role of the spinal ERK1 [?]/2 pathway in nociception are more intricate than suspected so far and that the GH/IGF-1 axis is an interesting new player in the regulation of spinal nociception. [2007] Glucocorticoid receptor [?]-dependent desensitization of 5-HT1A [?] autoreceptors by sleep deprivation: studies in GR-i transgenic mice. [2006] CONCLUSIONS: These data suggest that glucocorticoid-receptor [?] activation by corticosterone participates in the antidepressant-like adaptive changes in 5-HT1A [?] autoreceptors in sleep-deprived mice. [2006] In the current study, we used pharmacological inhibitors and dominant negative signaling constructs to delineate elements which participate in the activation of MAPK [?], a growth-associated mitogen-activated protein kinase, by human G protein-coupled 5-HT1A receptor transfected into CHO-K1 cells in a stable manner. [1996] Because clathrin-mediated endocytosis was required for 5-HT1A receptor-mediated Erk1/2 activation, we postulated a role for CAM in receptor endocytosis. [1999] These data demonstrate that the 5-HT1A receptor mediates MAPK [?] activity by convergence upon a common activation pathway that is shared with receptor tyrosine kinases. [1996] The selective 5-HT1A receptor ligand ipsapirone (IPS) induces corticotropin (ACTH) and cortisol secretion in humans. [1990] CONCLUSIONS: Major depressive disorder is associated with a widespread reduction in 5-HT1A receptor binding. [2000] BACKGROUND: Pharmacological and postmortem investigations suggest that patients with major depressive disorder have alterations in function or density of brain serotonin1A (5-HT1A) receptors. [2000] METHODS: Positron emission tomography with [carbonyl-11C]WAY-100635 was used to estimate regional 5-HT1A [?] binding potential (BP) in 28 medication-free MDD subjects. [2005] We determined 5-HT1A BP by PET and 5-HT1A C-1019G genotype in 43 controls and 22 medication-free MDD subjects. [2006] Serotonin 1A (5-HT1A) binding potential (BP) as assessed by positron emission tomography (PET) is higher in major depressive disorder (MDD) in association with the higher expressing GG genotype of the 5- HT1A C-1019G polymorphism. [2006] CONCLUSIONS: These data do not support previous findings of reduced 5- HT1A function in MDD and suggest that hypercortisolaemia or psychotropic medication may have accounted for the attenuation. [2003] RATIONALE: Several previous neuroendocrine studies have demonstrated reduced 5-HT1A receptor function in major depressive disorder (MDD). [2003] Inhibition of receptor endocytosis by use of sequestration-defective mutants of beta-arrestin1 and dynamin attenuated 5-HT1A receptor- stimulated Erk1/2 activation. [1999] Inhibitors of the classical CAM effectors myosin light chain kinase, CAM-dependent protein kinases II and IV, PP2B, and CAM-sensitive phosphodiesterase had no effect upon 5-HT1A receptor-mediated Erk1/2 activation. [1999] top Evidence suggests that the growth hormone (GH) response to L- tryptophan (L-TRP) is mediated by 5-HT1A receptors. [1999] 5-HT1A receptor binding and intracerebral activity in temporal lobe epilepsy: an [18F]MPPF-PET study. [2004] 5-HT1A receptor binding in temporal lobe epilepsy patients with and without major depression. [2007] RATIONALE AND OBJECTIVES: We previously found that the inhibition of median raphe nucleus (MRN) 5-HT transmission by local injections of a 5-HT1A agonist 8-OH-DPAT or corticotrophin-releasing factor (CRF) mimic the effect of foot shock stress to reinstate alcohol seeking. [2008] PET imaging of 5-HT1A receptor binding in patients with temporal lobe epilepsy. [2003] Monocyte-mediated suppression of IL-2-induced NK-cell activation. Regulation by 5-HT1A-type serotonin receptors. [1990] The effects of serotonin on baseline and IL-2-activated NK cells were mimicked by the 5-HT1A receptor-specific agonists 8-OH-DPAT and (+)- ALK. [1990] We conclude that serotonergic 5-HT1A receptors transduce signals that are required for NK cells to produce IFN-gamma in response to IL-2. [1993] These data supported the hypothesis that chronic NK1 receptor [?] blockade induces a functional desensitization of 5-HT 1A [?] autoreceptors similar to that observed with SSRIs. [2005] We now report that the 5-HT1A receptor agonist R(+)-8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT) is also capable of stimulating [3H] thymidine incorporation into SCLC GLC-8 cells, although with lower efficacy than 5-HT. [1995] We reject, however, the hypothesis that the effect of corticosterone on 5-HT1A responsiveness is mediated via altered RGS4 [?] or SGK1 mRNA expression. [2006] 5-HT1A receptors increase excitability of spinal motoneurons by inhibiting a TASK-1-like K+ current in the adult turtle. [2003] Our results show that activation of 5-HT1A receptors contributes to the excitatory effect of serotonin on spinal motoneurons by inhibition of a TASK-1 potassium channel leading to depolarization and increased input resistance. [2003] Inhibition of forskolin-stimulated cyclic AMP accumulation was measured in two stable HeLa cell lines HA6 and HA7 expressing different levels of recombinant human 5-HT1A receptors. [1997] On the other hand, the pretreatment with the 5HT1A agonist buspirone significantly enhanced the OT [?] response during hypoglycemia, without modifying the AVP rise. [1996] These results indicate that 5-HT1A receptor-mediated circuits located in the midline superior raphe system of the pigeon may play an important role in mechanisms controlling water intake, similar to that observed in mammals. [2005] ST-DEX after LT-ADX rapidly induced a recovery of 5-HT1A mRNA, Nissl labeling and CBD-IR in the granule cell layer. [1994] These data were highly correlated with results obtained at recombinant human 5-HT1A receptors in determinations of G-protein activation and inhibition of forskolin-stimulated adenylyl cyclase. [2005] Ras-dependent activation of fibroblast mitogen-activated protein kinase by 5-HT1A receptor via a G protein beta gamma-subunit- initiated pathway. [1996] Acceleration of proton efflux was not inhibited by sequestration of G protein betagamma-subunits, a maneuver that blocked 5-HT1A receptor activation of mitogen-activated protein kinase. [1997] top Agonist efficacy at 5-HT1A [?] receptors was determined for G-protein activation and adenylyl cyclase activity. [2005] GIRKs, as heteromultimers, compose the G protein-gated Kir (KG) channels, which are regulated by a variety of Gi/Go-coupled inhibitory neurotransmitter receptors such as m2-mus-carinic, serotonergic (5HT1A), GABAB, somatostatin and opioid (mu, delta, kappa) receptors. [1997] The Gi-coupled serotonin (5-hydroxytryptamine (5-HT)) 5-HT1A receptor, heterologously expressed in Chinese hamster ovary or human embryonic kidney 293 cells, mediated rapid activation of Erk1/2 via a mechanism dependent upon both Ras activation and clathrin-mediated endocytosis. [1999] Our data suggest that phosphatidylinositol 3-kinase and phosphatidylcholine-specific phospholipase C represent components of different, but partly overlapping pathways that can account almost entirely for the activation of ERK2 by the 5-HT1A receptor. [1996] At h5-HT1A receptors, stably transfected into Chinese Hamster Ovary Cells (CHO-h5-HT1A), the selective 5-HT1A receptor agonist, (+)8- hydroxy-dipropyl-amino-tetralin, ((+)8-OH-DPAT), transiently activated mitogen-activated protein kinase (MAPK [?]) with a pEC50 of 8. [2001] [Carbonyl-(11)C]WAY-100635 has been used extensively in positron emission tomography (PET) imaging of serotonin 1A receptors (5-HT1A) in vivo in the human brain. [2007] Neuroprotective efficacy of repinotan HCl, a 5-HT1A [?] receptor agonist, in animal models of stroke and traumatic brain injury [?]. [2005] Repinotan is a highly potent 5-HT1A [?] receptor agonist with strong neuroprotective efficacy in animal models of middle cerebral artery occlusion and traumatic brain injury [?]. [2005] The results demonstrated an association of aggressiveness with reduced 5-HT1A [?] receptor expression and function, thereby providing support for the view favoring the idea that brain [?] HT1A receptor contributes to the genetically defined individual differences in aggressiveness. [2005] 5-HT1A [?] receptor density, the receptor mRNA expression in brain [?] structures, and functional correlates for 5-HT1A [?] receptors identified as 8-OH-DPAT-induced hypothermia and lower lip retraction (LLR) were studied in Norway rats bred for 59 generations for the lack of aggressiveness and for high affective aggressiveness with respect to man. [2005] ECT-induced PRL [?] release: a 5-HT1A-mediated event? [1992] [3H]SCH 23390 (D1 receptor-selective), [3H]spiperone (D2 receptor- selective) and 8 OH [3H]DPAT (5-HT1A receptor-selective) were employed as radioligands in competition binding assays. [1998] Suggestions are made for enhancing selectivity at the 5-HT1A receptor or at the dopamine D2 receptor. [1993] Conformational and molecular mechanics studies of a new series of tricyclic ligands with affinity for either the dopamine D2 receptor or the 5-HT1A receptor, or both, has enabled us to elaborate considerably on previous pharmacophore models for these receptors. [1993] However, the clinical relevance may be clarified by the atypical antipsychotic drugs clozapine, quetiapine and ziprasidone which combine D2 receptor antagonism and 5-HT1A agonism. [2001] Thus, in CHO fibroblast cells, activation by the 5-HT1A receptor of ERK [?] and NHE share a number of overlapping features. [1998] However, our studies do not support a major role for ERK [?], when activated by the 5-HT1A receptor, as a short-term upstream regulator of NHE activity. [1998] Urapidil is an antihypertensive agent known to have central 5HT1A agonistic properties in addition to alpha-1 [?] blocking effects. [1994] This review summarizes results from experimental studies in rodents showing that in vivo galanin is a potent modulator of brain 5-HT transmission, and in particular 5-HT1A receptor-mediated functions. [2007] We conclude that CAM-dependent activation of Erk1/2 through the 5- HT1A receptor reflects its role in endocytosis of the receptor, which is a required step in the activation of MEK and subsequently Erk1/2. [1999] top Evaluation of EMD 128 130 occupancy of the 5-HT1A and the D2 receptor: a human PET study with [11C]WAY-100635 and [11C]raclopride. [2002] Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3- piperidinylpropan-2-ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 5. [2006] Studies toward the discovery of the next generation of antidepressants. Part 5: 3,4-Dihydro-2H-benzo[1,4]oxazine derivatives with dual 5-HT1A [?] receptor and serotonin transporter affinity. [2006] Studies towards the next generation of antidepressants. Part 4: derivatives of 4-(5-fluoro-1H-indol-3-yl)cyclohexylamine with affinity for the serotonin transporter and the 5-HT1A receptor. [2005] Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3- piperidinylpropan-2-ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 4. [2004] Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3- piperidinylpropan-2-ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 3. [2003] Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3- piperidinylpropan-2-ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 1. [2003] Specifically, we investigated two serotonin-related genes including three substitutions connected to human emotional states such as despondency and depression: the tryptophan hydroxylase (TPH) gene (A779C and A218C in the intron) and the serotonin1A (5-HT1A) receptor gene (Pro 16Leu in the cording region). [2004] For this process, we used two analytical procedures: (1) polymerase chain reaction (PCR) followed by single-strand conformational polymorphisms analysis for the A779C of TPH and the 5-HT1A receptor genes and (2) PCR followed by restriction fragment length polymorphism analysis for the A218C of TPH gene. [2004] Ipsapirone, a 5-HT1A agonist, suppresses REM sleep equally in unmedicated depressed patients and normal controls. [1996] To determine whether ipsapirone, a 5-HT1A agonist, differentially suppresses REM sleep in depressed patients compared with normal controls, we administered placebo, ipsapirone 10 mg, or ipsapirone 20 mg in a double-blind, random order before bedtime in 18 unmedicated patients with depression and 16 age-matched, gender-matched normal controls. [1996] Direct injection of a selective 5-HT1A agonist into the pedunculopontine tegmental nuclei reduces REM sleep, consistent with such a hypothesis. [1998] Systemic administration of 5-HT1A agonists consistently increases wakefulness, whereas slow wave sleep (SWS) and REM (rapid-eye movement) sleep are reduced. [1998] Microdialysis perfusion of a selective 5-HT1A agonist into the dorsal Raphe nucleus causes an increase in REM sleep, whereas the other sleep/wake stages are unaltered. [1998] These complex sleep/wake data of 5-HT1A ligands suggest that 5-HT1A receptor activation may increase waking, increase slow wave sleep or increase REM sleep depending on where the 5-HT1A receptors are located within the central nervous system. [1998] Systemic administration of the selective 5-HT1A receptor agonist 8- OHDPAT induces dose-dependent effects; i.e. low doses increase slow wave sleep and reduce waking, whereas large doses increase waking and reduce slow wave sleep and REM sleep. [2000] N-myc was amplified from 50- to 120-fold in eight of nine xenografts, clone 8 was amplified in five of the xenografts, and clone G21 was amplified in four of these five. [1987] The differential effects of EMD 128 130 at the D2 [?] and the 5-HT1A receptor (antagonist at D2 receptor, agonist at the 5-HTIA receptor) may explain the differences in occupancy observed. [2002] The receptors utilized were alpha 1 [?]-, alpha 2- and beta- adrenoceptors, adenosine 1, dopamine 1 and 2, muscarinic, Ca2+ channel, sulphonylureas, 5HT1, 5HT1A, 5HT2, histamine 1, benzodiazepine, opiate and Na+/K/ATPase [?]. [1997] OBJECTIVE: The present study investigated whether administration of a 5-HT1A receptor agonist would increase growth hormone (GH) and oxytocin levels in normal human subjects, and whether the responses would be modified according to the age and gender of the subjects. [1999] top The blunting of GH and psychological responses suggest that 5-HT1A receptor function is reduced by chronic fluvoxamine treatment. [1996] The 5-HT1A receptor gene was amplified by polymerase chain reaction and sequenced by the dideoxy method. [1995] 5-HT 1A receptors are reduced in temporal lobe epilepsy after partial- volume correction. [2005] Distinct temporal pattern of the effects of the combined serotonin- reuptake inhibitor and 5-HT1A agonist EMD 68843 on the sleep EEG in healthy men. [2001] RATIONALE: EMD 68843 (EMD) has properties of a serotonin (5-HT)- reuptake inhibitor and a partial 5-HT1A agonist in one molecule in order to combine antidepressive and anxiolytic properties. [2001] Overlapping PCR (polymerase chain reaction) fragments covered the whole coding sequence as well as the 5' untranslated region of the 5- HT1A gene. [1995] As specific therapeutic agents selective 5-HT1A agonists and cortisol or CRH antagonists are proposed. [1996] Selective postsynaptic 5-HT1A agonists together with CRH and/or cortisol antagonists are hypothesized to be a specific biological treatment for this depression type, in conjunction with psychological interventions to raise the stressor-threshold and to increase coping skills. [2001] Interestingly, we also determined by sequence analysis and detailed restriction mapping that G21 [?], previously isolated as a 'neuroblastoma-specific' cDNA clone from an MYCN amplicon, is a partial cDNA of DDX1. [1996] Stimulatory actions of corticosteroids involving GR occupation include increased responsiveness of hippocampal neurons to 5-HT1A receptor stimulation, attenuated autoinhibition of 5-HT, and a permissive effect on stress-induced increases in 5-HT release. [1998] Utilizing pulsed-field gel electrophoresis according to a method based on the combinatorial alignment of multiple single digests and a 5.5-megabase map surrounding the MYCN locus, we mapped the DDX1 gene within a 100 kb region about 400 kb upstream from the MYCN gene, where G21 is localized. [1996] Indoline and 1,2-benzisoxazole systems also provided potent 5-HT1F receptor agonists, and the 5-HT1A receptor selectivity of the indoline- and 1,2-benzisoxazole-based 5-HT1F receptor agonists could be improved with modification of the benzoyl moiety of the benzamides. [2004] Our data suggest that serotonin regulates NK-cell responsiveness to IL-2 via 5-HT1A receptors. [1990] Further hybridization experiments with both genes, complete sequencing of G21, and its comparison with that of the DDX1 gene eventually confirmed that the DDX1 gene is identical to G21. [1996] The results indicate that both NR1 subunit phosphorylation and the neurotrophin BDNF account, at least in part, for the neuroprotective effect of 8-OH-DPAT on cell damage induced by global ischemia in the gerbil hippocampus and support the potential interest of 5-HT1A receptor activation in the search for neuroprotective strategies. [2008] C57B/L6J mice were treated for 21 days with the selective NK1 receptor [?] antagonist GR 205171 (10 mg/kg daily) through subcutaneously implanted osmotic mini pumps, and DRN 5-HT 1A [?] autoreceptor functioning was assessed using various approaches. [2005] These include 5-HT1A receptor agonists, tachykinin receptor antagonists and various interventions within the hypothalamic- pituitary-adrenal system. [2006] EMD 128 130 is a novel compound acting as an agonist at the 5-HT1A receptor, and as an antagonist at the dopamine-2 (D2 [?]) receptor. [2002] The data thus suggest that, in contrast to previous theoretical proposals, 5-HT1A receptor antagonists provide no novel therapeutic approach to involuntary movement disorders such as dystonia. [1994] Several clinical and experimental findings suggest that abnormal serotonin (5-HT) function may be involved in movement disorders such as dystonia, and it was proposed that selective 5-HT1A receptor antagonists may be of benefit in treating such disorders. [1994] top In the present study, the novel, highly selective and silent 5-HT1A receptor antagonist (+)-WAY-100135 (N-tert-butyl-3(4-(2-methoxyphenyl) piperazin-1-yl)-2-phenylprop ionamide) was tested in an inbred line of Syrian hamsters with generalized dystonia, i.e. a frequent movement disorder in humans. [1994] CONCLUSIONS: Our data indicate that the patients with MJD are prone to manifest 5-HT1A receptor-associated symptoms, and tandospirone is a useful drug for these symptoms in patients with MJD, though a double-blind study is needed. [2004] BACKGROUND: We investigated the frequencies of the symptoms such as " ataxia, depression, insomnia, anorexia, and pain, " that have been reported to be associated with 5-HT1A receptor, and the effect of tandospirone citrate (tandospirone: 5-HT1A agonist) in patients with Machado-ph disease (MJD). [2004] Galanin, given intracerebroventricular (i.c.v.), was demonstrated to have strong inhibitory interactions with 5-HT1A receptor functions, particularly in the dorsal raphe but also in the hippocampus. [2007] Since pre- and postsynaptic 5-HT1A receptors in the dorsal raphe and hippocampus are implicated in the action of antidepressant drugs and in depressive disorders, it is suggested that galanin receptors may be an important target for development of novel antidepressant drugs. [2007] 1. The binding characteristics of tritium labeled 8-hydroxy-dipropyl- aminotetralin, or [3H]8-OH-DPAT, to the serotonin1A (5-HT1A) receptor in the stably transfected HeLa cell clone HA6 and in human cortical tissue were examined and compared. [1997] The modulation of learning and memory after left or right microinjections of the selective 5-HT1A [?] receptor agonist 8-OH- DPAT and of the 5-HT1A [?] receptor antagonist NAN190 into the hippocampal CA1 area of male Wistar rats was studied. [2007] We recently reported preliminary evidence that tandospirone citrate (tandospirone), a 5-HT1A agonist, improved cerebellar ataxia in patients with Machado-ph disease (MJD). [2005] Immunoglobulin inhibition was not specific for the 5HT1A receptor binding site, since immunoglobulins inhibited binding to 5HT2, D1, D2, and alpha 2-adrenergic binding sites. [1993] This reflects hyper-responsive 5-hydroxytryptamine type 1A (5HT1A) receptors in group A patients and may explain the presence of galactorrhoea in these patients despite normal basal and post-TRH prolactin levels. [1992] Monocyte-induced inhibition of IFN-gamma production was abrogated by the biogenic amine serotonin, acting via the 5-hydroxytryptamine, or serotonin (5-HT1A), subset of serotonin receptors (5-HTR). [1993] We here tested the hypothesis that corticosterone targets genes encoding RGS4 [?] or SGK1, which can both affect the 5-HT1A receptor associated Kir channel, thus affecting 5-HT1A receptor function. [2006] We conclude that the 5-HT1A receptor, which we have previously shown to stimulate phosphate uptake via protein kinase C, stimulates Na+/K+ ATPase [?] via a calcium-dependent mechanism. [1990] Plasma glucagon was measured by radioimmunoassay using an antiserum, G21 [?], specific for pancreatic glucagon. [1975] Placental tissues from rats on gestation days 14 (G14), 18 (G18) and 21 (G21) were used. [2005] Anxiolytic actions of the substance P (NK1 [?]) receptor antagonist L- 760735 and the 5-HT1A agonist 8-OH-DPAT in the social interaction test in gerbils. [2001] The putative 5-HT1A agonists 8-hydroxy-dipropylaminotetralin (DPAT), buspirone and p-aminophenylethyl-m-trifluoromethylphenyl piperazine (PAP [?]P) were tested for their ability to narrow the action potentials of bullfrog sensory neurons, a serotonergic response observed to be blocked by the 5-HT1A antagonists spiperone and spiroxitrine. [1988] The plasma glucagon levels measured by antiserum G 42 during an arginine test in five normal subjects were superposed on those obtained by other antiserum (G21), specific for pancreatic glucagon. [1979] For example, 8-OH-DPAT 5HT1A had an IC50 of 117 nM; TFMPP 5HT1B (2.3 microM0 and PAP [?]P 1A + 5HT2 (9 microM); ipsapirone 5HT1A (21.1 microM) and buspirone 5HT1A (greater than 100 microM); ketanserin 5HT2 (greater than 100 microM); 5-HT uptake inhibitors: paroxetine (13 nM); chlorimipramine (73 nM) and fluoxetine (653 nM). [1988] Under physiological fluctuations of corticosteroid concentrations, predominantly MR-mediated effects suppress the activity of the raphe- hippocampal system, notably serotonin (5-HT)1A receptor-related activity: 5-HT1A receptors are down-regulated, and the cellular response to 5-HT1A receptor activation is attenuated. [1998] top At a concentration of 10(-4) M at 72 hours the 5HT1A antagonist NAN- 190 hydrobromide and the 5-hydroxytryptamine1B antagonist SB224289 HCl (Tocris Laboratories, Bristol, United Kingdom) induced a 20% and 78% inhibitory effect, respectively, on PC3 [?] cell growth compared to that in controls (p < 0.0001). [2006] Other SSRIs, sertraline and fluvoxamine, also inhibited Kir4.1 channel currents whereas the tetracyclic (mianserin) or the 5-HT1A receptor-related (buspirone) antidepressants did not. [2007] The results suggest that the Q22 mutation confers increased amyloidogenic properties on the beta/A4 peptide, whereas the G21 mutation acts by a different pathogenic mechanism. [1993] Candidate genes excluded include those for tyrosine hydroxylase, the dopamine type 2 receptor, proenkephalin, the 5HT1A receptor and dopamine beta hydroxylase. [1993] Results precisely define base-pairing requirements for ribozyme helices 3 and 4, and identify eight essential nucleotides (G8, A9, A10, G21, A22, A23, A24 and C25) within the catalytic core of the ribozyme. [1993] These subjects were compared with 18 healthy control women (mean age, 25.1 +/- 5.8 years).Intervention The 5-HT1A receptor binding was measured using positron emission tomography imaging and a specific 5- HT1A receptor antagonist, [carbonyl-11C]WAY-100635. [2005] The stoichiometry of the phosphorylation was approximately 2 mol of [32P]ATP/mol of receptor, suggesting the involvement at least two of three putative PKC sites within the 5-HT1A receptor. [1991] Exclusion of the 5-HT1A serotonin neuroreceptor and tryptophan oxygenase genes in a large British kindred multiply affected with Tourette's syndrome, chronic motor tics, and obsessive-compulsive behavior. [1995] To identify this structural entity, we mutated Asn385 in the seventh transmembrane domain of the human 5-HT1A receptor, based on the observation that this residue is conserved in all 5-HT1A and beta- adrenergic receptors of different species but is absent in all other cloned guanine nucleotide-binding protein-coupled receptors. [1992] The lead compound was optimized following a strategy devised based on in silico 3D models and realized through an in silico-driven optimization process, rapidly overcoming selectivity issues (affinity to 5-HT1A [?] vs alpha1-adrenergic receptor) and potential cardiovascular issues (hERG [?] binding), leading to a clinical compound. [2006] The tri-ammine complex yielded ca. 40--90% of adducts, mono- and poly- platinated, bound to 4 guanines out of the 16 guanines in the sequence, in the decreasing amounts G9 > G15 >> G3 > G21 [?]. [2001] We also observed the 5-HT1A receptor localization in relaxin 3 positive neurons of the NI. [2008] We found that 6 out of 10 sera of non-autistic children with an abnormal EEG recognized the second extracellular loop of the 5-HT1A receptor. [1998] Serotonin, by acting on the astroglial 5-HT1A receptor, releases S- 100 [?] beta and regulates neuronal morphology and apoptosis. [2002] No significant differences across C(-1019)G 5-HT1A genotype groups were found for TCI temperament and character traits and for NEO FFI personality scales. [2006] Several neurochemicals (glutamate, glycine receptors, choline acetyltransferase, serotonin, norepinephrine, and thyrotropin- releasing hormone [?]) increase expression with age, while others (GABA, serotonin receptor 1A, substance P, neurokinin 1 receptor, and somatostatin) decrease their expression. [2005] Excitation of 36 with near UV light in the presence of the single- stranded target 34-mer, 5'T G A C C A T C A A T A A G14 G A A G18 A A G21 [?] C C C T T C A G C G G C C3' 1 caused oxidative damage at guanine bases, leading to alkali-labile sites which were monitored by polyacrylamide gel electrophoresis. [2004] Therefore to determine the range of reaction, a series of 'variant' targets was prepared, in which G21 [?] was replaced with a cytosine and a guanine substituted for a base further towards the 3'-end (e.g. Variant 3; 5'T G A C C A T C A A T A A G G A A G A A C C G23 C T T C A G C G G32 C C3 [?]'). [2002] Monocyte 5-HT1A receptors mediate pindobind suppression of natural killer cell activity: modulation by catalase. [2001] Monocyte-induced suppression of resting and IFN-activated NK cells was abrogated by the biogenic amines histamine [via H2-type receptors (H2R)] and serotonin [via 5-HT1A-type receptors (5-HT1AR)]. [1992] top A gain of chromosomes was seen in the groups C7, C8, C10, D14, F19, F20, G21, G22. [1991] Moreover, the genotype distributions of the TPH and 5-HT1A receptor genes were compared between Akita Prefecture and other prefectures, but no significant differences were found. [2004] Amplification of IMR-32 clones 8, G21, and N-myc in human neuroblastoma xenografts. [1987] Amplification of clones 8, G21, and N-myc, which were derived from human neuroblastoma cell lines IMR-32 and NB-19, were studied in nine neuroblastoma xenografts. [1987] This xenograft is known to have a homogeneously staining region (HSR) on chromosome 20 and to exhibit 60- to 100-fold amplification of clones 8, G21 and N-myc [?], and showed a rapid tumor weight doubling time of 5.9 days; it represents one of the most malignant strains of human neuroblastoma. [1993] However, strains G21 [?] and G30 were unusual because they expressed intimin alpha and had a restricted tissue tropism of intimin gamma phenotype. [2002] Four enteropathogenic Escherichia coli (EPEC) strains belonging to the O55 serogroup (G21 [?] and G30 [both O55:H6], G35 [O55:H-], and G58 [O55:H7]) were tested for their tissue tropism by using human intestinal in vitro organ culture. [2002] In the hairpin, G21 [?] and U42 can be UV cross-linked. [2001] Our results provide direct evidence that, during RNA-protein recognition, Tat is in close proximity to O6 of G21 and G26 in the major groove of TAR RNA. [1998] A 36-nt RNA fragment containing the photoreactive domain but lacking the substrate binding domain also cross-links with high efficiency and maps between G21 and U41, as observed with the intact molecule. [1994] Quote Link to comment Share on other sites More sharing options...
Guest guest Posted April 26, 2008 Report Share Posted April 26, 2008 Is that what salvia divinorum hits, kappa-b? Some people experience an anti-depressant afterglow as described here: Antidepressant Effects of the Herb Salvia Divinorum: A Case Report Karl R. Hanes, PhD Journal of Clinical Psychopharmacology 2001;21:634-635 Editors: Case Report Ms. G is a 26-year-old woman with a history of depression that has shown no significant periods of remission since adolescence and has been predominated by feelings of worthlessness, lack of interest in social activities, an absence of occupational satisfaction, and inability to find " purpose and meaning " in her life. After first seeking treatment for her depression 5 years ago Ms. G was prescribed sertraline, 50 mg daily, which she self-discontinued after 3 months, reporting no significant benefits. Ms. G then underwent a course of cognitive-behavioural therapy for about 6 months, with some improvement but no definitive resolution of her symptoms. Hamilton Depression Rating Scale (HAM-D 1 ) scores during the 6-month period of cognitive-behavioural therapy were consistently in the moderately depressed range (i.e. 19–21). During a review consultation some 7 months after discontinuing cognitive-behavioural therapy Ms. G claimed to have found relief from her symptoms of depression with use of the herb salvia divinorum sourced through a mail-order herbal supplier. A HAM-D score of 2 confirmed remission of her symptoms of depression at this time. Ms. G claims that she discovered its antidepressant effects accidentally after smoking the herb and had later developed a method of oral consumption which she claimed maintained its antidepressant effects even after she abstained from using it for up to a week. Despite being cautioned against use of a herb whose safety profile was unknown, she has continued to use a preparation of salvia divinorum leaves taken as an oral dose of 2–3 leaves (1/2 to 3/4 of a gram of leaf material) three times per week (the leaves are chewed and held in the mouth for 15–30 minutes). During this period she has continued to show a total remission of her symptoms of depression according to HAM-D scores in the range of 0–2 and has maintained this improvement for the last 6 months, showing no signs of relapse and reporting only minimal side effects, such as occasional lightheadedness for up to 1 hour after using the herb. Ms. G volunteered that she has also benefited from occasional intoxicating oral doses of salvia divinorum, consisting of from 8–16 leaves of the herb (approximately 2 to 4 grams), claiming that this herb had engendered a kind of " psychospiritual " awakening, characterized by the discovery of the depth of her sense of self, greater self-confidence, increased feelings of intuitive wisdom and " connectedness to nature. " Discussion Salvia divinorum is a perennial herb of the Labiateae (mint) family native to the Sierra Mazateca region of Oaxaca, Mexico. 2–4 Its main constituents have been identified as the neoclerodane diterpenes Salvinorin A and B 5,6 while trace elements of several other diterpenes have also been detected. 6 The plant has been used in healing ceremonies by the Mazatec Indians of Oaxaca for centuries and for the treatment of such conditions as anaemia, headache, and rheumatism. 7 The psychoactive effects of the main ingredient Salvinorin A in humans were uncovered recently and it has enjoyed some popularity since that time as a legal, short-acting psychedelic, though its psychoactivity varies considerably depending on dosage and method of ingestion. 8 This unique case may be of interest to the psychiatric and psychopharmacological communities in demonstrating the possible therapeutic effects of the unique active components of salvia divinorum in a case of treatmentresistant depression. While the typical dose used by this patient in maintenance management of her depression, consisting of 2–3 leaves, is well below that reported to cause significant intoxication when taken orally, 8 one cannot discount the possibility that some of the benefits derived from salvia divinorum were due to the psychedelic qualities associated with the larger doses of this herb used occasionally by this patient. While a discussion of these effects is outside the scope of this paper, the value of psychedelic compounds as research tools and their beneficial effects in the amelioration of symptoms of psychiatric conditions is well established. 9–11 Given that the mechanisms of action of the constituents of salvia divinorum remain unknown and the spectrum of psychedelic effects of this herb appears to be unique, 8 it is not inconceivable that research using the active ingredients from this herb may pinpoint a unique mechanism of antidepressant action for these compounds. This, in turn, could lead to methods for the management of depression or of treatment-resistant subtypes of this condition. This possibility is further enhanced by the recent finding using the screening procedure called Novascreen that Salvinorin A did not show significant inhibition of reference target compounds on any of the 42 known bioreceptors tested. 8 We may be dealing with a highly novel agent that has significant research and therapeutic potential in fields such as psychopharmacology, psychiatry and complementary disciplines such as herbal medicine. Karl R. Hanes, PhD Cognitive-Behavioural Treatment Centre, Melbourne, , Australia > > Hi everyone, i've just found out that 5ht1a receptors are upregulated > by kappa-b. > > Kappa-b is enhanced by Melanin and also by tolerance to one of the > chemicals in pasturised milk. > > I will try to find out more about this if I can. > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted April 27, 2008 Report Share Posted April 27, 2008 I think kappa-b is an enzyme, whereas salvia acts upon the kappa receptors, which i think are opiate receptors. But I will have a look to see whether or not this is true. Quote Link to comment Share on other sites More sharing options...
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