Inhibition of calmodulin - regulated calcium pump activity in rat brain by toxaphene

In vivo effects of toxaphene on calcium pump activity in rat brain synaptosomes was studied. Male Sprague-Dawley rats were dosed with toxaphene at 0,25,50, and 100 mg/kg/day for 3 days and sacrificed 24 h after last dose. Ca2+-ATPase activity and 45Ca uptake were determined in brain P2 fraction. Toxaphene inhibited both Ca2+-ATPase activity and 45Ca2+ uptake and the inhibition was dose dependent. Both substrate and Ca2+ activation kinetics of Ca2+-ATPase indicated non-competitive type of inhibition as evidenced by decreased catalytic velocity but not enzyme-substrate affinity. The inhibited Ca2+-ATPase activity and Ca2+ uptake were restored to normal level by exogenously added calmodulin which increased both velocity and affinity. The inhibition of Ca2+-ATPase activity and Ca2+ uptake and restoration by calmodulin suggests that toxaphene may impair active calcium transport mechanisms by decreasing regulator protein calmodulin levels