Jpn. J. Pharmacol. 70 (3), 259-267 (1996)

Endothelin ETA and ETB Receptors Mediate Endothelin-1-Induced Apamin-Sensitive Relaxation in the Guinea Pig Ileum

Li-Hua Shan (1), Mariko Nishiyama (1,*), Tadao Shibasaki (1), Kayoko Moroi (1), Katsutoshi Goto (2), Tomoh Masaki (3) and Sadao Kimura (1)

(1) Division of Cardiovascular Biology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan (2) Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305, Japan (3) Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606, Japan (*) To whom correspondence should be addressed.

Abstract: Endothelin (ET) receptors involved in ET-1-induced responses of the longitudinal muscle of the isolated guinea pig ileum were studied. ET-1 caused concentration-dependent contractions, while ET-3 and selective ETB-receptor agonists, IRL1620 and sarafotoxin 6c (S6c), showed little or no effect. The ET- 1-induced contractions were antagonized by BQ-123, an ETA-receptor antagonist, or PD142893, an ETA/ ETB-receptor antagonist, indicating that the contraction is mediated by the ETA receptor. In preparations precontracted with carbachol, ET-1 elicited relaxations at lower concentrations and contractions at higher concentrations. ET-3, IRL1620 and S6c caused relaxations. These relaxations were little affected by BQ-123, but greatly antagonized by PD142893. The ET-1-induced relaxations were slightly affected by BQ-788, an ETB-receptor antagonist, but were markedly inhibited by the combination of BQ-788 and BQ-123. In ETB receptor-desensitized preparations, ET-1-induced relaxations were antagonized by BQ-123, whereas ET-3, S6c and IRL1620 showed no response. All these relaxations were abolished by apamin. These results indicate that ETA and ETB receptors mediate relaxation of the ileal smooth muscle through activation of apamin-sensitive K+ channels.

Keywords: Endothelin, Endothelin receptor, Apamin, Relaxation, Ileal smooth muscle (guinea pig)

Copyright© The Japanese Pharmacological Society 1996

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