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

[Guest guest]

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!

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> talking to myself here probably, but just for the record

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> Biochem Pharmacol. 2003 May 15;65(10):1741-6.

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> Interaction of dimercaptosuccinic acid (DMSA) with angiotensin II on

> calcium mobilization in vascular smooth muscle cells.

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> 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.

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> Toxicology. 1999 Nov 5;138(2):81-91.

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> Meso-2,3-dimercaptosuccinic acid induces calcium transients in cultured

> rhesus monkey kidney cells.

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> 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.

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