2,3-dimercaptopropanol inhibits Ca2+ transport in microsomes from brain but not from fast-skeletal muscle

Ca2+ is involved in the regulation of a variety of physiological processes, but a persistent increase in free cytosolic Ca2+ concentrations may contri bute to cell injury. Dimercaprol (BAL) is a compound used in the treatment of mercury intoxication, but presents low therapeutic efficacy. The molecul ar mechanism responsible for the BAL toxicity is poorly known. In the prese nt study, the effect of BAL and inorganic and organic mercury on Ca2+ trans port by Ca2+-ATPases located in the sarco/endoplasmic reticulum of fast-ske letal muscle and brain was examined. Ca2+ uptake by brain and fast-skeletal muscle microsomes was inhibited in a dose-dependent manner by Hg2+. The ca lculated IC50 for Ca2+ uptake inhibition by HgCl2 was 1.05 +/- 0.09 muM (n = 8) for brain and 0.72 +/- 0.06 muM (n = 9) for muscle. The difference was significant at p < 0.01 (data expressed as mean +/- SD). At a low concentr ation (I muM), 2,3-dimercaptopropanol had no effect on Ca2+ uptake by brain or muscle vesicles and did not abolish the inhibition caused by Hg2+. A hi gh concentration of BAL (I mM) nearly abolished the inhibition caused by 1. 75 muM HgCl2 or 6 muM CH3HgCl in skeletal muscle. Surprisingly, at intermed iate concentrations (40-100 muM) BAL partially inhibited Ca2+ transport in brain but had no effect on muscle. Furthermore, ATP hydrolysis by brain or muscle microsomes was not inhibited by BAL. These results suggest that in b rain microsomes BAL affects in a different way Ca2+ transport and ATP hydro lysis. The increase in BAL concentration observed after toxic administratio n of this compound to experimental animals may contribute to deregulate Ca2 + homoeostasis and, consequently, to the neurotoxicity of BAL.