Cyclosporin A affects functions concerning acetylcholine release of cholinergic Torpedo synaptosomes

The effect of cyclosporin A was investigated on Torpedo synaptosomes. Cyclosporin A inhibits KCl-evoked acetylcholine release (up to 50% at 1 mu M) and was inactive on acetylcholine release induced by a Ca2+ ionophore, A23187. Interestingly, when the synaptosomes were pretreated with cyclosporin A, this immunosuppressor did abolish the modulation of A23187-induced acetylcholine release produced by two other drugs, cetiedil (alpha-cyclohexyl-3-thienyl acetic acid 2-(hexahydro-1H-azepin-1-yl) ethyl ester, citrate salt) and MR16728 (N-(N'-hexamethylene imino)-propyl-phenyl-cyclohexyl-methyl acetamide, chlorhydrate), which were previously shown to be inhibitory and stimulatory, respectively. Moreover, cyclosporin A and MR16728 are competitive inhibitors of [3H]cetiedil binding to purified synaptosomal presynaptic membranes (dissociation constant of 181.9 nM). These results suggest that presynaptic proteins involved in acetylcholine release (directly or indirectly through cyclophilin) are potential targets of cyclosporin A in Torpedo synaptosomes.