Inhibition by Quinacrine of Depolarization-Induced Acetylcholine Release and Calcium Influx in Rat Brain Cortical Synaptosomes

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Abstract
The effects of quinacrine on depolarization-induced [3H]acetylcholine (ACh) release and 45Ca2+ influx were examined in rat brain cortical synaptosomes. Quinacrine significantly reduced the stimulated release of [3H]ACh by high K+ and veratridine without affecting the spontaneous efflux from the preloaded synaptosomes. Quinacrine had no effect on ionophore A23187-induced release of [3H]ACh from the synaptosomes. Quinacrine (100 microM) markedly diminished the stimulated Ca2+ influx by veratridine and high K+ but not that by "Na+-free." Trifluoperazine, a potent calmodulin antagonist, inhibited both Ca2+ influx and ACh release induced by the depolarizing agents. Inhibitory potencies of the two drugs on ACh release and Ca2+ influx were compared with the antagonism of calmodulin by two drugs, suggesting that the inhibition of depolarization-induced Ca2+ influx and ACh release by these drugs could not be explained by the antagonism of calmodulin.