Moorthy K S, Trottman C H, Spann C H, Desaiah D
J Toxicol Environ Health. 1987;20(3):249-59. doi: 10.1080/15287398709530979.
In vivo effect of toxaphene on calcium pump activity in rat brain P2 fraction was studied. Male Sprague-Dawley rats (200-250 g) were dosed with toxaphene at 0, 25, 50, and 100 mg/kg X d for 3 d and sacrificed 24 h after last dose. Ca2+-ATPase activity and 45Ca2+ uptake were determined in brain P2 fraction. Toxaphene decreased both Ca2+-ATPase activity and 45Ca2+ uptake, and the reduction was dose-dependent. Both substrate and Ca2+ activation kinetics of Ca2+-ATPase indicated noncompetitive type of inhibition, as evidenced by decreased catalytic velocity but not enzyme-substrate affinity. The decreased Ca2+-ATPase activity and 45Ca2+ uptake were restored to normal level by exogenously added calmodulin, which increased both velocity and affinity. The inhibition of Ca2+-ATPase activity and 45Ca2+ uptake and restoration by calmodulin suggests that toxaphene may impair active calcium transport mechanisms by decreasing levels of calmodulin.
研究了毒杀芬对大鼠脑P2组分中钙泵活性的体内效应。选用体重200 - 250克的雄性斯普拉格-道利大鼠，分别以0、25、50和100毫克/千克×天的剂量给予毒杀芬，持续3天，并在末次给药后24小时处死。测定脑P2组分中的Ca2 + - ATP酶活性和45Ca2 +摄取量。毒杀芬降低了Ca2 + - ATP酶活性和45Ca2 +摄取量，且这种降低呈剂量依赖性。Ca2 + - ATP酶的底物和Ca2 +激活动力学均表明为非竞争性抑制类型，表现为催化速度降低但酶 - 底物亲和力未降低。外源性添加钙调蛋白可使降低的Ca2 + - ATP酶活性和45Ca2 +摄取量恢复至正常水平，这增加了速度和亲和力。Ca2 + - ATP酶活性和45Ca2 +摄取量的抑制以及钙调蛋白的恢复表明，毒杀芬可能通过降低钙调蛋白水平来损害主动钙转运机制。
