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Review article: effects of the 5‐HT 3 receptor antagonist alosetron on neuromuscular transmission in canine and human intestinal muscle
Author(s) -
Audolfsson G.,
Bayguinov O.,
Yamamoto T.,
Somogyi G.T.,
Schraut W.H.,
Sanders K.M.,
Bauer A.J.
Publication year - 1999
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.1999.00004.x-i2
Subject(s) - medicine , bethanechol , neuromuscular transmission , excitatory postsynaptic potential , acetylcholine , atropine , irritable bowel syndrome , cholinergic , endocrinology , neurotransmission , neuromuscular junction , antagonist , migrating motor complex , muscarinic acetylcholine receptor , receptor , stomach , neuroscience , biology
Background: Currently, therapeutic treatments for irritable bowel syndrome fail to produce significant clinical results. We hypothesized that alosetron, a selective 5‐HT 3 antagonist, may provide symptomatic relief in irritable bowel syndrome patients through a decrease in the amplitude of gastrointestinal contractions. Aim: To determine the in vitro effect of alosetron on neuromuscular transmission in the canine and human jejunal and colonic muscularis externa. Results: Alosetron diminished electrical field‐stimulated (EFS) contractions recorded from muscles of the canine and human small and large intestines. Mechanistically, the diminished EFS response could be explained by the ability of alosetron to decrease the fractional release of 14 C‐choline radiolabelled acetylcholine evoked by EFS from human jejunal muscle. The inhibition of EFS contractions was not limited to atropine‐sensitive events, as non‐cholinergic excitatory EFS evoked contractions were also inhibited. Additionally, alosetron at high concentrations (> 30 μ m ) directly altered bethanechol stimulated contractions. Conclusion: Caution must be used in the interpretation of these data because significant alterations in EFS‐induced contractions were only observed with large pharmacological concentrations of alosetron, and the response was not selective for cholinergically‐mediated excitatory neuromuscular transmission.