A POTENT AND SPECIFIC AGONIST, SUC-[GLU9,ALA11,15]-ENDOTHELIN-1(8-21), IRL-1620, FOR THE ETB RECEPTOR

A series of C-terminal linear peptides of endothelin (ET)-1 and their Nα-succinyl (Suc) analogs were synthesized and their binding affinities for the two subtypes of ET receptor, ETA and ETB, in porcine lung membranes were examined. Among the synthetic analogs, Suc-[Glu9, Ala11,15]-ET-1(8-21), IRL 1620, was the most potent and specific ligand for the ETB receptor ( KiETA KiETB ≅ 120,000) as judged by the Ki values for ETA (1.9 μM) and ETB (16 pM) receptors. IRL 1620 was 60 times more selective for the ETB receptor than ET-3 ( KiETA KiETB ≅ 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 ETB receptor agonist. © 1992.