RE: Re: these are the types of studies that we need to know the relevance of...

[Guest guest]

This is what I was reading about in the neurotransmitter book - there are about 10 different calcium channels and blocking any of them produces a different behaviour (often autistic)

> To: Autism-Biomedical-Europe > Date: Fri, 26 Nov 2010 20:38:53 +0000> Subject: Re: these are the types of studies that we need to know the relevance of...> > Err I'm listening and I think this would deplete dopamine in a lot of cases? If CA2 signals blocked. Hence some of the symptoms of autism? Yes I'm extremely interested....> Possible?> Please keep posting!> > >> > > > talking to myself here probably, but just for the record> > > > > > > > Biochem Pharmacol. 2003 May 15;65(10):1741-6.> > > > Interaction of dimercaptosuccinic acid (DMSA) with angiotensin II on> > calcium mobilization in vascular smooth muscle cells.> > > > Kramer HJ, Mensikova V, Bäcker A, Meyer-Lehnert H, Gonick HC.> > Department of Medicine, Renal Section, Medizinische> > Universitäts-Poliklinik, Wilhelmstrasse 35-37, University of Bonn,> > D-53111, Bonn, Germany.> > > > Dimercaptosuccinic acid (DMSA) was shown to lower blood pressure in rat> > models of arterial hypertension. Thus, there is evidence that-besides> > its chelating properties-DMSA has a direct vascular effect, e.g. through> > scavenging of reactive oxygen species (ROS). We speculated that, in> > addition, intracellular calcium mobilization may be involved in this> > action. Therefore, the present study examined the effects of DMSA on> > Ca(2+) mobilization in cultured vascular smooth muscle cells (VSMCs)> > from rat aorta. Intracellular free Ca(2+) concentration ([Ca(2+)](i))> > was measured with fura-2 AM. In a first series of experiments DMSA,> > 10(-11) to 10(-6)M, induced an immediate dose-dependent up to 4-fold> > rise of [Ca(2+)](i) (P<0.001) which was almost completely blunted by the> > calcium channel blocker verapamil or the intracellular calcium release> > blocker TMB-8. In a second series of experiments, when VSMCs were> > exposed acutely to DMSA (10(-11) to 10(-6)M), the angiotensin (ANG) II> > (10(-8)M)-induced rise in [Ca(2+)](i) to 295+/-40nM was attenuated at> > the average by 49% independent of the dose of DMSA. Preincubation of> > VSMCs with DMSA (10(-6)M) for 60min reduced basal [Ca(2+)](i) by 77%> > (P<0.001) and dose-dependently attenuated the ANG II (10(-8)M)-induced> > rise in [Ca(2+)](i) between 28 and 69% at concentrations between 10(-9)> > and 10(-5)M DMSA, respectively (P<0.05 and <0.01). In the presence of> > TMB-8, which attenuated the ANG II (10(-8)M)-induced rise in [Ca(2+)](i)> > by 66%, DMSA (10(-6)M) had no additional suppressive effect on> > [Ca(2+)](i). The results suggest that DMSA acutely raises [Ca(2+)](i) by> > stimulating transmembrane calcium influx via L-type calcium channels and> > by calcium release from intracellular stores followed by a decrease in> > [Ca(2+)](i) probably due to cellular calcium depletion. Thus, in> > addition to its action as scavenger of ROS, which in part mediate the> > vasoconstrictor response, e.g. to ANG II, DMSA may exert its hypotensive> > effect through decreasing total cell calcium, thereby attenuating the> > vasoconstrictor-induced rise in [Ca(2+)](i) in VSMCs.> > > > > > Toxicology. 1999 Nov 5;138(2):81-91.> > > > Meso-2,3-dimercaptosuccinic acid induces calcium transients in cultured> > rhesus monkey kidney cells.> > > > Pokorski PL, Department of Pharmaceutical Sciences, Institute of> > Chemical Toxicology, Wayne State University, Detroit, MI 48201, USA.> > > > The maintenance of intracellular Ca2+ homeostasis is critical to many> > cellular functions that rely on the calcium ion as a messenger. While> > attempting to characterize the effects of lead on intracellular calcium> > levels ([Ca2+]i) in LLC-MK2 Rhesus Monkey kidney cells, we observed that> > treatment with the metal chelating drug, meso-2,3-dimer-captosuccinic> > acid (DMSA) evoked transient increases in [Ca2+]i. Changes in [Ca2+]i> > were monitored using the Ca2+ indicator dye Fura-2 and a dual wavelength> > fluorescence imaging system. In the presence of 2 mM extracellular Ca2+,> > DMSA treatment caused a concentration-dependent (15-500 microM)> > transient increase in [Ca2+]i returning to baseline levels within 30-60> > s. Pharmacologic concentrations of DMSA (30 microM) stimulated a> > three-fold increase in [Ca2+]i, which was spatiotemporally comparable to> > Ca2+ transients induced by other calcium agonists. Depletion of inositol> > trisphosphate (IP3)-sensitive [Ca2+]i stores with the smooth endoplasmic> > reticulum calcium-ATPase (SERCA) inhibitor thapsigargin did not prevent> > DMSA-elicited increases in [Ca2+]i, suggesting that Ca2+ mobilized by> > DMSA was either extracellular or from an non-IP3 releasable Ca2+ pool.> > Treatment with glutathione, cysteine, or 2-mercaptoethanol caused> > similar but not identical calcium transients. Adenosine-5'-trisphosphate> > (ATP) also elicited transient increases in [Ca2+]i similar to those of> > DMSA. No transient increases in [Ca2+]i were elicited by DMSA or ATP in> > the absence of extracellular calcium. These data indicate that DMSA and> > other sulfhydryl compounds trigger an influx of extracellular calcium,> > suggesting a previously unobserved and unanticipated interaction between> > DMSA and the Ca2+ messenger system.> >> > > > > ------------------------------------> > DISCLAIMER> No information contained in this post is to be construed as medical advice. If you need medical advice, please seek it from a suitably qualified practitioner.>