Pharmacological Heterogeneity of Both Endothelin ETA- and ETB-Receptors in the Human Saphenous Vein

The Japanese Journal of Pharmacology

Mariko Nishiyama³  Nobuyuki Nakajima¹  Tomoh Masaki²  Sadao Kimura³  Yoshiharu Takahara¹ 

[1] The First Department of Surgery, Chiba University School of Medicine;Department of Pharmacology, Faculty of Medicine, Kyoto University;Division of Cardiovascular Biology, Center for Biomedical Science, Chiba University School of Medicine

关键词: Endothelin;    Sarafotoxin;    Saphenous vein (human);    Endothelin receptor;    Endothelin receptor antagonist;   

DOI  :  10.1254/jjp.69.391

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(27)Cited-By(9)To study endothelin receptor subtypes that mediate the smooth muscle contraction of human saphenous vein, effects of some endothelin-receptor agonists and antagonists were examined. Endothelin (ET)-1 and sarafotoxin 6b (S6b) elicited potent concentration-dependent contractions with similar pD2 values and similar maximal responses. Selective ETB-receptor agonists, sarafotoxin 6c (S6c) and IRL1620 (Suc-[Glu9, Ala11, 15]-endothelin-1(8-21)), also caused contractions, but their maximal responses were about one third of that of ET-1. ET-3 showed a biphasic concentration-response curve. An ETA-receptor antagonist, BQ-123 (cyclo(-D-Asp-L-Pro-D-Val-L-Leu-D-Trp-)), an ETA/ETB-receptor antagonist, PD142893 (Ac-D-Dip-Leu-Asp-Ile-Ile-Trp), or the combination of these two antagonists hardly affected the contractile effect of ET-1, while each of them markedly antagonized the effects of higher concentrations of ET-3 and S6b. Contractions induced by lower concentrations of ET-3 and S6b were resistant to these antagonists. The concentration-response curves for S6c and IRL1620 were not affected by BQ-123. The effect of IRL1620 was markedly inhibited by PD142893, while S6c-induced contractions were much more resistant to PD142893. These different sensitivities to antagonists suggested heterogeneity of both ETA- and ETB-receptors [ETA1 (sensitive to BQ-123), ETA2 (resistant to BQ-123), ETB1 (sensitive to PD142893) and ETB2 (resistant to PD142893)] in the human saphenous vein, although contractions mediated by ETB-subtypes have smaller maximal responses than those mediated by the ETA-subtypes.

【 授权许可】

Unknown