Urade Y, Fujitani Y, Oda K, Watakabe T, Umemura I, Takai M, Okada T, Sakata K, Karaki H
International Research Laboratories, CIBA-GEIGY Ltd., Takarazuka, Japan.
FEBS Lett. 1992 Oct 12;311(1):12-6. doi: 10.1016/0014-5793(92)81355-p.
In the inhibition of specific binding of [125I]endothelins (ETs) to membrane from various tissues of rats, guinea pigs, pigs and humans, [Cys11-Cys15]-ET-1(11-21), IRL 1038, has a much higher affinity for ETB receptors (Ki = 6-11 nM) than for ETA receptors (Ki = 0.4-0.7 microM). In contraction assays, with ET-3 as a stimulant, 3 microM IRL 1038 antagonized the ETB receptor-mediated contraction of guinea pig ileal and tracheal smooth muscle without any significant agonistic activity, but did not effect the ETA receptor-mediated contraction of rat aortic smooth muscle. IRL 1038 is therefore, considered to be the first antagonist selective to the ETB receptor.
在抑制[125I]内皮素（ETs）与大鼠、豚鼠、猪和人类各种组织的细胞膜特异性结合方面，[Cys11 - Cys15]-ET-1(11 - 21)，即IRL 1038，对ETB受体的亲和力（Ki = 6 - 11 nM）远高于对ETA受体的亲和力（Ki = 0.4 - 0.7 microM）。在收缩试验中，以ET - 3作为刺激剂，3 microM的IRL 1038拮抗了ETB受体介导的豚鼠回肠和气管平滑肌收缩，且无任何明显的激动活性，但对ETA受体介导的大鼠主动脉平滑肌收缩无影响。因此，IRL 1038被认为是首个对ETB受体具有选择性的拮抗剂。
