Involvement of cyclooxygenase-dependent pathway in contraction of isolated ileum by urotensin II.
We previously reported that urotensin II induced biphasic (brief- and long-lasting) contractions and the brief contraction was mediated by acetylcholine release from ganglionic cholinergic neurons in a segment of guinea-pig ileum. In the present work, we studied the mechanism contributing to long-lasting contractions induced by urotensin II. Treatment with 0.1 microM tetrodotoxin, 300 nM omega-conotoxin GVIA (an inhibitor of N-type Ca2+ channels) and 10 microM indomethacin (an inhibitor of cyclooxygenases) markedly inhibited 100 nM urotensin II-induced long-lasting contractions. The addition of 1 microM prostaglandin F2alpha (PGF2alpha) caused a limited brief contraction following long-lasting contraction, while 1 microM PGE2 induced marked biphasic contractions. Treatment with neurotoxins inhibited the long-lasting contractions induced by PGF2alpha and PGE2 without changing the PGE2-induced brief contractions. Treatment with 1 microM atropine markedly inhibited the urotensin II- and PGF2alpha-induced long-lasting contractions, but was less effective on the PGE2 responses. Treatment with a phospholipase A2 inhibitor decreased the urotensin II-induced contractions. These findings suggest that urotensin II induces, at least partially, long-lasting contractions via PG-sensitive cholinergic neurons and muscarinic acetylcholine receptors in the ileum.
Horie
Syunji
S
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
Tsurumaki
Yuumi
Y
Someya
Akiyoshi
A
Hirabayashi
Tetsuya
T
Saito
Takeshi
T
Okuma
Yasunobu
Y
Nomura
Yasuyuki
Y
Murayama
Toshihiko
T
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014579:Urotensins / Q000494:pharmacology*; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D018727:Muscarinic Antagonists; D014579:Urotensins; D013779:Tetrodotoxin; D001285:Atropine; C029677:urotensin II; D020866:omega-Conotoxin GVIA; D015237:Dinoprost; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D007213:Indomethacin