Meso-2,3-dimercaptosuccinic acid induces calcium transients in cultured rhesus monkey kidney cells.
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.
Pokorski
P L
PL
Department of Pharmaceutical Sciences, Institute of Chemical Toxicology, Wayne State University, Detroit, MI 48201, USA.
McCabe
M J
MJ
Pounds
J G
JG
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002614:Chelating Agents / Q000633:toxicity*; D005456:Fluorescent Dyes; D016257:Fura-2; D006706:Homeostasis; D015759:Ionomycin / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008253:Macaca mulatta; D008856:Microscopy, Fluorescence; D010084:Oxidation-Reduction; D004113:Succimer / Q000633:toxicity*
D002614:Chelating Agents; D005456:Fluorescent Dyes; D015759:Ionomycin; D000255:Adenosine Triphosphate; D004113:Succimer; D002118:Calcium; D016257:Fura-2