Inhibition by quinacrine of depolarization-induced acetylcholine release and calcium influx in rat brain cortical synaptosomes.
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.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014701:Veratridine / Q000494:pharmacology
D014701:Veratridine; D011796:Quinacrine; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium