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© 1986 Oxford University Press

research-article

Toxaphene Inhibition of Calmodulin-Dependent Calcium ATPase Activity in Rat Brain Synaptosomes

K. S. PRASADA RAO*, C. H. TROTTMAN{dagger}, W. MORROW{dagger} and D. DESAIAH*

*Department of Neurology, University of Mississippi Medical Center Jackson, Mississippi 39216 {dagger}Department of Chemistry, Jackson State University Jackson, Mississippi 39217

Toxaphene Inhibition of Calmodulin-Dependent Calcium ATPase Activity in Rat Brain Synaptosomes. PRASADA RAO, K. S., TROTTMAN, C. H., MORROW, W., AND DESAIAH, D. (1986) Fundam. Appl. Toxicol. 6, 648–653. Effect of toxaphene on Ca+2-ATPase activity in rat brain synaptosomes was studied in vitro and in vivo. Ca+2-ATPase in calmodulin-depleted synaptosomes was inhibited in vitro to a maximum of about 50% at 150 µM toxaphenc. Substrate activation kinetics of Ca+2-ATPase in synaptosomes revealed that toxaphene inhibited the enzyme activity noncompetetively by decreasing Vmax values, without affecting the enzyme-substrate affinity. Toxaphene inhibited the calmodulin activated Ca+2-ATPase activity in a concentration-dependent manner with an IC50 of 10 µM, a concentration at which no significant effect was observed on basal enzyme activity. Nuclear and P2 fraction (synaptosomes) calmodulin levels were reduced significantly in toxaphene-treated rats. The synaptosomal Ca+2-ATPase was also reduced to about 45% in toxaphene-treated rats and the activity was restored to normal levels by the exogenously added calmodulin. These results suggest that toxaphene may cause synaptic dysfunction by in terfering with calmodulin and its regulation of neuronal calcium.


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