Meso-2,3-dimercaptosuccinic acid induces calcium transients in cultured rhesus monkey kidney cells |
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Authors: | Pokorski P L McCabe M J Pounds J G |
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Institution: | Department of Pharmaceutical Sciences, Institute of Chemical Toxicology, Wayne State University, Detroit, MI 48201, USA. |
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Abstract: | 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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