Lindane (gamma-hexachlorocyclohexane) induces internal Ca2+ release and capacitative Ca2+ entry in Madin-Darby canine kidney cells

The effect of lindane (gamma -hexachlorocyclohexane), an organochlorine pes ticide, on Ca2+ mobilization in Madin-Darby canine kidney cells was examine d by fluorimetry using fura-2 as a Ca2+ indicator. Lindane (5-200 muM) incr eased [Ca2+](i) concentration-dependently. The [Ca2+](i) signal comprised a n immediate initial rise followed by a persistent phase. Ca2+ removal inhib ited the [Ca2+](i) signal by reducing both the initial rise and the sustain ed phase. This implies lindane-triggered Ca2+ influx and Ca2+ release. In C a2+-free medium, 0.15 mM lindane increased [Ca2+](i) after pretreatment wit h carbonylcyanide m-chlorophenylhydrazone (CCCP; 2 muM), a mitochondrial un coupler, and two endoplasmic reticulum Ca2+ pump inhibitors, thapsigargin a nd 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 store s. La3+ (1 mM) partly inhibited 0.1 mM lindane-induced [Ca2+](i) increase, confirming that lindane induced Ca2+ influx. Addition of 3 mM Ca2+ increase d [Ca2+](i) after pretreatment with 0.15 mM lindane for 750 sec. in Ca2+-fr ee medium, which indicates lindane-induced capacitative Ca2+ entry. Lindane (0.15 mM)-induced Ca2+ release was not reduced by inhibiting phospholipase C with 2 muM U73122, but was inhibited by 70% by the phospholipase A(2) in hibitor aristolochic acid (40 muM).