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In favour of the vesicular hypothesis: neurochemical evidence that vesamicol (AH5183) inhibits stimulation‐evoked release of acetylcholine from neuromuscular junction
Author(s) -
Vizi E.S.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb14619.x
Subject(s) - acetylcholine , stimulation , neuromuscular junction , neurochemical , chemistry , endocrinology , neuroscience , biology
1 The effects of optical isomers of vesamicol (2‐(4‐phenylpiperidino) cyclohexanol), an inhibitor of acetylcholine (ACh) storage, on stimulation‐evoked release of [ 3 H]‐acetylcholine ([ 3 H]‐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 [ 3 H]‐choline. This method made it possible to detect exclusively the Ca o ‐dependent release of [ 3 H]‐ACh in response to stimulation, and therefore to test the vesicular hypothesis. 2 (−)−Vesamicol was approximately 20 times more potent than (+)‐vesamicol in reducing stimulation‐evoked release of [ 3 H]‐ACh. 3 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. 4 The fact that (−)−vesamicol inhibited the release of [ 3 H]‐ACh in response to electrical stimulation only when it was administered prior to the loading of the tissue with [ 3 H]‐choline, and had no effect when the stores had already been filled with labelled [ 3 H]‐ACh indicates that the stimulation‐evoked release of [ 3 H]‐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.