In vitro effect of lead on Ca(2+)-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 Ca(2+)-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 Ca(2+)-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 Ca(2+)-ATPase of synaptic plasma membranes and microsomes of cerebral cortex and cerebellum in a concentration-dependent manner. The IC50 values of Ca(2+)-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 Ca(2+)-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 Ca(2+)-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 microM) inhibits inositol 1,4,5-triphosphate-mediated Ca2+ uptake and release in microsomes of rat cerebellum.
Bettaiya
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R
Division of Natural Sciences, Selma University, Alabama 37601, USA.
Yallapragada
P R
PR
Hall
E
E
Rajanna
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002531:Cerebellum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007854:Lead / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009942:Organometallic Compounds / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology
D009942:Organometallic Compounds; D007854:Lead; C029891:lead chloride; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; C008261:lead acetate; D002118:Calcium