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 contribute to cell injury. Dimercaprol (BAL) is a compound used in the treatment of mercury intoxication, but presents low therapeutic efficacy. The molecular mechanism responsible for the BAL toxicity is poorly known. In the present study, the effect of BAL and inorganic and organic mercury on Ca2+ transport by Ca2+-ATPases located in the sarco/endoplasmic reticulum of fast-skeletal muscle and brain was examined. Ca2+ uptake by brain and fast-skeletal muscle microsomes was inhibited in a dose-dependent manner by Hg2+. The calculated IC50 for Ca2+ uptake inhibition by HgCl2 was 1.05+/-0.09 microM (n = 8) for brain and 0.72+/-0.06 microM (n = 9) for muscle. The difference was significant at p < 0.01 (data expressed as mean +/- SD). At a low concentration (1 microM), 2,3-dimer-captopropanol had no effect on Ca2+ uptake by brain or muscle vesicles and did not abolish the inhibition caused by Hg2+. A high concentration of BAL (1 mM) nearly abolished the inhibition caused by 1.75 microM HgCl2 or 6 microM CH3HgCl in skeletal muscle. Surprisingly, at intermediate concentrations (40-100 microM) 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 brain microsomes BAL affects in a different way Ca2+ transport and ATP hydrolysis. The increase in BAL concentration observed after toxic administration of this compound to experimental animals may contribute to deregulate Ca2+ homoeostasis and, consequently, to the neurotoxicity of BAL.
Quinhones
E B
EB
Departamento de Quimica, Centro de Ciencias naturais e Exatas, Universidade Federal de Santa Maria. erridison@zipmail.com.br
Souza
D O
DO
Rocha
J B
JB
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004112:Dimercaprol / Q000633:toxicity*; D017136:Ion Transport; D008861:Microsomes / Q000378:metabolism*; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D051381:Rats
D004112:Dimercaprol; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D002118:Calcium