In vivo effects of toxaphene on calmodulin-regulated calcium-pump activity in rat brain

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.