title: In vitro effect of lead on Ca(2+)-ATPase in synaptic plasma membranes and microsomes of rat cerebral cortex and cerebellum.
abstract: 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.
authors.affiliation: Division of Natural Sciences, Selma University, Alabama 37601, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bettaiya
authors.forename: P R
authors.initials: PR
authors.lastname: Yallapragada
authors.forename: E
authors.initials: E
authors.lastname: Hall
authors.forename: S
authors.initials: S
authors.lastname: Rajanna
mesh_terms: 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
chemical_list: 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