Demonstration of a receptor in Torpedo synaptic vesicles for the acetylcholine storage blocker L-trans-2-(4-phenyl(3,4-3H)-

Transport and storage of acetylcholine by purified Torpedo electric organ synaptic vesicles is blocked by the drug L-trans-2-(4-phenylpiperidino)cyclohexanol (AH- 5183). This study sought evidence of a specific receptor for the drug. Highly tritiated L-trans-2-(4-phenyl(3,4-3H)piperidino)- cyclohexanol (L-(3H)AH5183) was synthesized. An excess of nonradioactive L-isomer competed with L-(3H)AH5183 for binding to purified Torpedo synaptic vesicles whereas nonra- dioactive D-isomer did so poorly. Dissociation of bound L- (3H)AH5183 was first order with a rate constant at 23?C of 0.23 ? 0.03 min-', and association was too rapid to study. At equilibrium the amount of L-(3H)AH5183 bound at saturation varied in different vesicle preparations, but in one typical