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

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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.