An endothelin B receptor-selective antagonist: IRL 1038, [Cys 11-Cys 15]-endothelin-1(11–21)

Abstract

In the inhibition of specific binding or [ 125]endothelins (ETs) to membranes from various tissues of rats, guinea pigs, pigs and humans, [Cys 11-Cys 15]-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.