The effects of optical isomers of vesamicol (2-(4-phenylpiperidino) cyclohexanol), an inhibitor of acetylcholine (ACh) storage, on stimulation-evoked release of [3H]-acetylcholine [3H]-ACh) from the neuromuscular junction have been studied in the region of the mouse hemidiaphragm which contains the motor endplates, and which can easily be loaded with [3H]-choline. This method made it possible to detect exclusively the Ca0-dependent release of [3H]-ACh in response to stimulation, and therefore to test the vesicular hypothesis. (-)-Vesamicol was approximately 20 times more potent than (+)-vesamicol in reducing stimulation-evoked release of [3H]-ACh. 4-Aminopyridine, a potassium channel blocker, enhanced the release of ACh in response to stimulation, but failed to increase release from hemidiaphragm which had been pretreated with (-)-vesamicol. The fact that (-)-vesamicol inhibited the release of [3H]-ACh in response to electrical stimulation only when it was administered prior to the loading of the tissue with [3H]-choline, and had no effect when the stores had already been filled with labelled [3H]-ACh indicates that the stimulation-evoked release of [3H]-ACh is of vesicular origin and (-)-vesamicol has no effect on the release process. This is the first neurochemical evidence for the vesicular origin of stimulation-evoked release of ACh from the neuromuscular junction.
|Number of pages||5|
|Journal||British journal of pharmacology|
|Publication status||Published - Jan 1 1989|
ASJC Scopus subject areas