In vitro effect of lead on Ca2+-ATPase in synaptic plasma membranes and microsomes of rat cerebral cortex and cerebellum

Earlier investigations from this laboratory suggest that lead interferes with the calcium homeostasis of rat brain through modulation of an inositol polyphosphate second-messenger system. The present investigation was initiated to study the comparative effects of lead chloride and lead acetate on synaptosomal and microsomal Ca2+-ATPase of rat cerebral cortex and cerebellum in vitro. The synaptic plasma membranes and microsomes were prepared by using sucrose gradient (1.2-0.8 M). The assay of Ca2+-ATPase was done by hydrolysis of ATP and the liberated inorganic phosphate was estimated. Both lead chloride and lead acetate at micromolar concentrations significantly inhibited the Ca2+-ATPase of synaptic plasma membranes and microsomes of cerebral cortex and cerebellum in a concentration-dependent manner. The IC50 values of Ca2+-ATPase for both lead salts in synaptosomes were significantly lower (P < 0.05) than that of microsomes, indicating more sensitivity. Significantly (P < 0.05) lower IC50 values for both synaptosomal and microsomal Ca2+-ATPase were obtained for lead acetate than for lead chloride. The results suggest that lead acetate is more potent than lead chloride in inhibiting the Ca2+-ATPase. The microsomal Ca2+ uptake was also studied in cerebellum and cerebral cortex in the presence of different concentrations of both the lead salts. However, these lead salts in vitro did not reveal a significant (P < 0.05) change in the microsomal Ca2+ uptake of cerebellum and cerebral cortex. But earlier investigations indicated that in vitro lead (0.25-2 mu M) inhibits inositol 1,4,5-triphosphate-mediated Ca2+ uptake and release in microsomes of rat cerebellum. (C) 1996 Academic Press, Inc.