An endothelin B receptor-selective antagonist: IRL 1038, [Cys11-Cys15]-endothelin-1(11-21)
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.
Urade
Y
Y
International Research Laboratories, CIBA-GEIGY Ltd., Takarazuka, Japan.
Fujitani
Y
Y
Oda
K
K
Watakabe
T
T
Umemura
I
I
Takai
M
M
Okada
T
T
Sakata
K
K
Karaki
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D003553:Cystine; D004220:Disulfides; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D008024:Ligands; D008566:Membranes / Q000378:metabolism; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009928:Organ Specificity; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017466:Receptors, Endothelin / Q000378:metabolism*; D012680:Sensitivity and Specificity; D017386:Sequence Homology, Amino Acid; D013552:Swine
D004220:Disulfides; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D008024:Ligands; D010446:Peptide Fragments; D017466:Receptors, Endothelin; C077420:Cys(11)-Cys(15)-endothelin-1 (11-21); D003553:Cystine