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 interfer es with the calcium homeostasis of rat brain through modulation of an inositol polyphosphate second-messenger system. The present investigat ion was initiated to study the comparative effects of lead chloride an d lead acetate on synaptosomal and microsomal Ca2+-ATPase of rat cereb ral cortex and cerebellum in vitro. The synaptic plasma membranes and microsomes were prepared by using sucrose gradient (1.2-0.8 M). The as say of Ca2+-ATPase was done by hydrolysis of ATP and the liberated ino rganic 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 cerebe llum in a concentration-dependent manner. The IC50 values of Ca2+-ATPa se for both lead salts in synaptosomes were significantly lower (P < 0 .05) than that of microsomes, indicating more sensitivity. Significant ly (P < 0.05) lower IC50 values for both synaptosomal and microsomal C a2+-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 studi ed in cerebellum and cerebral cortex in the presence of different conc entrations of both the lead salts. However, these lead salts in vitro did not reveal a significant (P < 0.05) change in the microsomal Ca2uptake of cerebellum and cerebral cortex. But earlier investigations i ndicated that in vitro lead (0.25-2 mu M) inhibits inositol 1,4,5-trip hosphate-mediated Ca2+ uptake and release in microsomes of rat cerebel lum. (C) 1996 Academic Press, Inc.