RT Journal Article SR Electronic T1 Subtype selectivity of a novel endothelin antagonist, FR139317, for the two endothelin receptors in transfected Chinese hamster ovary cells. JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 127 OP 131 VO 43 IS 2 A1 I Aramori A1 H Nirei A1 M Shoubo A1 K Sogabe A1 K Nakamura A1 H Kojo A1 Y Notsu A1 T Ono A1 S Nakanishi YR 1993 UL http://molpharm.aspetjournals.org/content/43/2/127.abstract AB We investigated the receptor-binding properties and the antagonist activities of FR139317, a novel endothelin (ET) antagonist, in transfected Chinese hamster ovary cells permanently expressing the two ET receptor subtypes (ETA and ETB). In displacement analysis using membrane preparations derived from the receptor-expressing cells, FR139317 showed a high affinity for ETA (Ki = 1 nM) and a lower affinity for ETB (Ki = 7.3 microM). FR139317 inhibited ETA-mediated phosphatidylinositol hydrolysis and arachidonic acid release and produced a parallel shift in the dose-response curve for ET-1, with respective pA2 values of 8.2 and 7.7. In contrast, FR139317 had no inhibitory effects on these ET-1-induced responses in ETB-expressing cells. FR139317 itself showed no stimulatory effects on phosphatidylinositol hydrolysis and arachidonic acid release in ETA- and ETB-expressing cells. Thus, FR139317 is a potent, competitive, and highly selective antagonist for ETA. This compound should be a powerful tool for investigation of the physiological properties of ETA and exploration of its role in diseases.