title: Effect of lead on the biological activity of calmodulin in rat brain.
abstract: In the present investigation, we observed that lead in vitro activates calmodulin at lower concentrations, and the maximum activation was observed at 30 microM concentration. In vivo lead exposure (50 mg/kg body weight, intragastrically) for a period of 8 weeks also stimulated the activity of calmodulin by 45%. The addition of trifluoperazine resulted in partially inhibiting the lead-stimulated calmodulin activity, whereas the calcium-stimulated calmodulin activity was completely inhibited by trifluoperazine. Studies with purified calmodulin from the brain of control and lead-treated animals indicate that approximately 4 mole of calcium was present bound/mole of calmodulin in control animals and this fraction was reduced in lead-treated animals to approximately 3 mole of calcium/mole of calmodulin. Lead distribution revealed that approximately 68% of the total lead present was bound to calmodulin and the remaining 32% present was bound to non-calmodulin binding sites following lead exposure. These results indicate that in vivo lead exposure is able to displace and mimic the action of calcium and this may constitute a molecular mechanism of lead neurotoxicity.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: R
authors.initials: R
authors.lastname: Sandhir
authors.forename: K D
authors.initials: KD
authors.lastname: Gill
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D007854:Lead / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014268:Trifluoperazine / Q000494:pharmacology
chemical_list: D002147:Calmodulin; D014268:Trifluoperazine; D007854:Lead; D002118:Calcium