Contraction of isolated guinea-pig ileum by urotensin II via activation of ganglionic cholinergic neurons and acetylcholine release

Urotensin II and its receptor are expressed in the gastrointestinal tract of mice, but the effects of urotensin II on the gastrointestinal functions have not been established. In the present study, we investigated the effects of human urotensin II on a segment of the,guinea-pig ileum. The addition of urotensin II induced contraction of the ileum in concentration-manner (-log EC50 value was 8.13 +/- 0.21). The response by urotensin II was extracellular CaCl2-dependent and easily desensitized. Like nicotine, the contraction induced by 100 nM urotensin II was inhibited by treatment with atropine, hexamethonium, D-tubocurarine, tetrodotoxin or hemicholinium-3. and enhanced by physostigmine. Treatment with omega-conotoxin GVIA (an inhibitor of N-type Ca2+ channels, 300 nM) inhibited 100 nM urotensin II- and 4 muM nicotine-, but not 3 muM acetylcholine-, induced contraction. Both urotensin II and nicotine stimulated [H-3]choline release in a tetrodotoxin-sensitive manner from the prelabeled slices of the ileum. These findings suggest that urotensin II stimulated acetylcholine release from the ganglionic cholinergic neurons and thus stimulated contraction via muscarinic acetylcholine receptors in the guinea-pig ileum. Urotensin II receptor system in the myenteric neurons may regulate the gastrointestinal functions. (C) 2003 Elsevier Ltd. All rights reserved.