Biochemical and pharmacological profile of a potent and selective endothelin B-receptor antagonist, BQ-788

摘要: We describe the characteristics of a potent and selective endothelin (ET) B-receptor antagonist, BQ-788 [N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D -1- methoxycarbonyltryptophanyl-D-norleucine]. In vitro, this compound potently competitively inhibits 125I-labeled 1 (ET-1) binding to ETB receptors on human Girardi heart cells (IC50, 1.2 nM) but only poorly ETA neuroblastoma cell line SK-N-MC 1300 nM). isolated rabbit pulmonary arteries, shows no agonist activity up 10 microM antagonizes vasoconstriction induced by an ETB-selective agonist, BQ-3020 (pA2, 8.4). rat, ETA-selective BQ-123 (1 mg/kg, i.v.), does not affect transient depressor response ET-1 (0.3 nmol/kg, i.v.) following sustained pressor response; vice versa, abolishes response, resulting in rapid onset apparently enhanced response. Thus, being receptor may be considered as powerful tool for investigating role ET physiological pathological processes.