title: Biochemical evidence that acetylcholine release from cholinergic nerve terminals is mostly vesicular.
abstract: The nature of the intraterminal compartments from which acetylcholine (ACh) is released following presynaptic stimulation was investigated. This was pursued by examining the effects of the anticholinergic drug 2-(4-phenylpiperidino)cyclohexanol (AH5183) on the release of newly synthesized [3H]ACh and of endogenous ACh from purified cholinergic nerve terminals (synaptosomes) which were isolated from the electric organs of Torpedo. Preincubation of the synaptosomes, with AH5183 (1-10 microM), does not affect either the intraterminal synthesis of [3H]ACh or the uptake of its precursors, but results in a marked inhibition (85%) of the release of the newly synthesized [3H]ACh. However, when AH5183 is added following the accumulation of [3H]ACh in the nerve terminals, it does not affect [3H]ACh release. AH5183 also has no effect on the release of preformed endogenous ACh. These findings, together with the previous in vitro demonstrations that AH5183 is a potent inhibitor of ACh uptake into isolated cholinergic vesicles, suggest that most of the synaptosomal ACh is secreted by a vesicular mechanism.
mesh_terms: D000085:Acetates / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004557:Electric Organ / Q000378:metabolism; D066298:In Vitro Techniques; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000494:pharmacology; D010880:Piperidines; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D013574:Synaptosomes / Q000378:metabolism; D014101:Torpedo
chemical_list: D000085:Acetates; D010880:Piperidines; C006189:vesamicol; D010622:Phencyclidine; D000109:Acetylcholine