EFFECT OF LEAD ON THE BIOLOGICAL-ACTIVITY OF CALMODULIN IN RAT-BRAIN

In the present investigation, we observed that lead in vitro activates calmodulin at lower concentrations, and the maximum activation was observed at 30 mu M 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. (C) 1994 Academic Press, Inc.