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 EC(50) value was 8.13+/-0.21). The response by urotensin II was extracellular CaCl(2)-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 Ca(2+) channels, 300 nM) inhibited 100 nM urotensin II- and 4 microM nicotine-, but not 3 microM acetylcholine-, induced contraction. Both urotensin II and nicotine stimulated [(3)H]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.
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan.
Syunji
S
Horie
Satoko
S
Yasuda
Yuumi
Y
Tsurumaki
Akiyoshi
A
Someya
Takeshi
T
Saito
Yasunobu
Y
Okuma
Yasuyuki
Y
Nomura
Tetsuya
T
Hirabayashi
Toshihiko
T
Murayama
D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D005726:Ganglia, Parasympathetic / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D014579:Urotensins / Q000494:pharmacology*; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018722:Nicotinic Agonists; D014579:Urotensins; D009538:Nicotine; C029677:urotensin II; D020866:omega-Conotoxin GVIA; D002122:Calcium Chloride; D002794:Choline; D000109:Acetylcholine