Calcium channel activity in rat brain synaptosomes: effects of neuroleptics and other factors regulating phosphorylation and transmitter release.
Neuroleptic drugs inhibit depolarization-induced Ca uptake in nerve endings, having IC50 values in the micromolar range. Dopamine and a variety of other substances including opiates and PGE1 are inactive. The effect is probably not mediated by the interaction of the neuroleptics with calmodulin, which itself is a potent inhibitor of stimulated Ca uptake. Dibutyryl cyclic AMP, but not fluoride, increases K+-stimulated Ca uptake. Phosphatidic acid, which is an intermediate in transmitter-stimulated phosphatidylinositol turnover, acts as a Ca ionophore in nerve endings and enhances K+-stimulated Ca uptake at a relatively low concentration. Carbamyl choline, a known stimulator of phosphatidylinositol turnover, did not, however, cause a significant increase in K+-stimulated Ca uptake. Treatment of the nerve ending fraction with relatively small amounts of phospholipase A2 greatly inhibited depolarization-induced Ca uptake, demonstrating the importance of phospholipids for the functioning of the potential-dependent Ca channel in nerve endings. These studies suggest that the regulation of voltage-sensitive Ca channels in nerve endings may be one mechanism controlling transmitter release.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D002116:Calcitonin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002122:Calcium Chloride / Q000378:metabolism; D002147:Calmodulin / Q000494:pharmacology; D002417:Cattle; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D014150:Antipsychotic Agents; D002147:Calmodulin; D007473:Ion Channels; D002116:Calcitonin; D002122:Calcium Chloride; D002118:Calcium