title: Effects of vesicular acetylcholine uptake blockers on frequency augmentation-potentiation in frog neuromuscular transmission.
abstract: Vesamicol inhibits the vesicular loading of acetylcholine molecules. The effects of vesamicol and similarly acting compounds on neuromuscular transmission in frogs were investigated to determine whether these inhibitors-inhibit the frequency augmentation-potentiation of transmitter release. Various vesicular acetylcholine transport blockers suppressed the stimulation frequency-related release parameter, k, in a dose-dependent manner. Artane, cetiedil, chloroquine, ethodin, quinacrine, vesamicol and its benzyl-analogue, 2-(4-benzylpiperidino)cyclohexanol, had strong effects, while those of aminacrine, chlorpromazine, fluphenazine, imipramine, pyrilamine and thioridazine were weak. A significant correlation was observed between the biochemically reported values of IC50 and the electrophysiological inhibitory potencies on k at 20 microM. Contrary to expectations from the biochemical data, however, vesamicol and its benzyl-analogue showed equipotent inhibitory actions on the electrophysiological frequency augmentation-potentiation relation. Low sensitivity and low selectivity of the frequency augmentation-potentiation for vesamicol and its benzyl-analogue lead us to conclude that the vesicular acetylcholine transporter is not the site of the electrophysiological action of vesamicol and similarly acting chemicals.
authors.affiliation: Department of Physiology, Shimane Medical University, Izumo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Maeno
authors.forename: K
authors.initials: K
authors.lastname: Enomoto
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004975:Ethacridine / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D011898:Ranidae; D012044:Regression Analysis; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D000928:Antidepressive Agents; D001381:Azepines; D009467:Neuromuscular Depolarizing Agents; D010880:Piperidines; C006189:vesamicol; C006955:cetiedil; D002738:Chloroquine; D011796:Quinacrine; D011738:Pyrilamine; D000109:Acetylcholine; D004975:Ethacridine