An endothelin B receptor‐selective antagonist: IRL 1038, [Cys11‐Cys15]‐endothelin‐1(11–21)

FEBS Letters

Sakata, Kiyoshi¹  Takai, Michihiro²  Watakabe, Tadashi²  Fujitani, Yasushi²  Okada, Toshikazu²  Umemura, Ichiro²  Urade, Yoshihiro²  Kiraki, Hideaki¹  Oda, Kyoko² 

[1] Department of Veterinary Pharmacology, Faculty of Agriculture, The University of Tokyo, Bunkyo-ku, Tokyo 113, Japan;International Research Laboratories, CIBA-GEIGY (Japan) Ltd., 10-66 Miyuki-cho, Takarazuka 665, Japan

关键词: Endothelin;    Receptor;    Antagonist;    Smooth muscle;    Contraction;    ET;    endothelin;    DSS;    disuccinimidyl suberate;    HPLC;    high performance liquid chromatography;    HEPES;    N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid;    K i;    apparent binding inhibition constant;    EC50;    the concentration inducing half maximum contraction;   

DOI  :  10.1016/0014-5793(92)81355-P

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In the inhibition of specific binding or [¹²⁵]endothelins (ETs) to membranes from various tissues of rats, guinea pigs, pigs and humans, [Cys¹¹-Cys¹⁵]-ET-1(11–21), IRL 1038, has a much higher affinity for ET_B receptors (K _i = 6–11 nM) than for ET_A receptors (K _i = 0.4–0.7 μM). In contraction assays, with ET-3 as a stimulant, 3 μM IRL 1038 antagonized the ET_B receptor-mediated contraction of guinea pig ileal and tracheal smooth muscle without any significant agonistic activity, but did not effect the ET_A receptor-mediated contraction of rat aortic smooth muscle. IRL 1038 is, therefore, considered to be the first antagonist selective to the ET_B receptor.

【 授权许可】

Unknown