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Lu CH, Lee KC, Chen YC, Cheng JS, Yu MS, Chen WC, Jan CR: Lindane (gamma-hexachlorocyclohexane) induces internal Ca2+ release and capacitative Ca2+ entry in Madin-Darby canine kidney cells. Pharmacol Toxicol. 2000 Oct;87(4):149-55.
The effect of lindane (gamma-hexachlorocyclohexane), an organochlorine pesticide, on Ca2+ mobilization in Madin-Darby canine kidney cells was examined by fluorimetry using fura-2 as a Ca2+ indicator. Lindane (5-200 microM) increased [Ca2+] i concentration-dependently. The [Ca2+] i signal comprised an immediate initial rise followed by a persistent phase. Ca2+ removal inhibited the [Ca2+] i signal by reducing both the initial rise and the sustained phase. This implies lindane-triggered Ca2+ influx and Ca2+ release. In Ca2+ -free medium, 0.15 mM lindane increased [Ca2+] i after pretreatment with carbonylcyanide m-chlorophenylhydrazone (CCCP, 2 microM), a mitochondrial uncoupler, and two endoplasmic reticulum Ca2+ pump inhibitors, thapsigargin and cyclopiazonic acid. Conversely, pretreatment with lindane abolished CCCP- and thapsigargin-induced Ca2+ release. This suggests that 0.15 mM lindane released Ca2+ from the endoplasmic reticulum, mitochondria and other stores. La3+ (1 mM) partly inhibited 0.1 mM lindane-induced [Ca2+] i increase, confirming that lindane induced Ca2+ influx. Addition of 3 mM Ca2+ increased [Ca2+] i after pretreatment with 0.15 mM lindane for 750 sec. in Ca2+ -free medium, which indicates lindane-induced capacitative Ca2+ entry. Lindane (0.15 mM)-induced Ca2+ release was not reduced by inhibiting phospholipase C with 2 microM U73122, but was inhibited by 70% by the phospholipase A2 inhibitor aristolochic acid (40 microM). |
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