A potent and specific agonist, Suc-[Glu9, Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptor

Abstract A series of C-terminal linear peptides of endothelin (ET)-1 and their N α -succinyl (Suc) analogs were synthesized and their binding affinities for the two subtypes of ET receptor, ET A and ET B , in porcine lung membranes were examined. Among the synthetic analogs, Suc-[Glu 9 , Ala 11,15 ]-ET-1(8-21), IRL 1620, was the most potent and specific ligand for the ET B receptor ( Ki ETA Ki ETB ≅ 120,000 ) as judged by the Ki values for ET A (1.9 μM) and ET B (16 pM) receptors. IRL 1620 was 60 times more selective for the ET B receptor than ET-3 ( Ki ETA Ki ETB ≅ 1,900 ). IRL 1620 (10 −9 –10 −7 M) induced contractions of the guinea pig trachea with a comparable potency to those of ET-1 or ET-3, suggesting that IRL 1620 is a potent ET B receptor agonist.