In favour of the vesicular hypothesis: Neurochemical evidence that vesamicol (AH5183) inhibits stimulation-evoked release of acetylcholine from neuromuscular junction

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Abstract

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.

Original languageEnglish
Pages (from-to)898-902
Number of pages5
JournalBritish Journal of Pharmacology
Volume98
Issue number3
Publication statusPublished - 1989

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Neuromuscular Junction
Acetylcholine
Choline
vesamicol
Potassium Channel Blockers
Motor Endplate
4-Aminopyridine
Electric Stimulation

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "In favour of the vesicular hypothesis: Neurochemical evidence that vesamicol (AH5183) inhibits stimulation-evoked release of acetylcholine from neuromuscular junction",
abstract = "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.",
author = "E. V{\'i}zi",
year = "1989",
language = "English",
volume = "98",
pages = "898--902",
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