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

[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.

[学科分类] 生物化学/生物物理

[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