Calcium channel activity in rat brain synaptosomes: Effects of neuroleptics and other factors regulating phosphorylation and transmitter release

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Abstract
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 voltagesensitive Ca channels in nerve endings may be one mechanism controlling transmitter release.