title: Novel antagonist of endothelin ETB1 and ETB2 receptors, BQ-788: effects on blood vessel and small intestine.
abstract: The effects of a peptide, BQ-788 [N-cis-2, 6-dimethyl-piperidinocarbonyl-L-gamma-methylleucyl-D-1- methoxycarbonyltryptophanyl-D-norleucine], on isolated blood vessel and small intestine were examined. In the rat aorta, BQ-788 antagonized the endothelium-dependent, ETB1 receptor-mediated relaxation due to endothelin (ET)-3 with EC50 of 3 microM. In the rat aorta without endothelium, 10 microM BQ-788 weakly antagonized the ETA1-mediated contractile effects of ET-1 and ET-3. In the rabbit saphenous vein, it has been shown that ETA1, ETA2, ETB1 and ETB2 receptors mediate contraction. BQ-788 (10 microM) almost completely inhibited the contractile effect of sarafotoxin S6c (an ETB1 and ETB2 agonist). BQ-788 also antagonized the contractile effect of ET-3 (an ETA1, ETB1 and ETB2 agonist) more strongly than desensitization of ETB1 and ETB2 receptors. However, BQ-788 did not antagonize the effect of ET-1 (agonist of all four receptors). In the guinea pig ileum, 10 microM BQ-788 completely inhibited the relaxation mediated by ETB1 and ETB2 receptors. These results suggest that BQ-788 is a novel antagonist of ETB1 and ETB2 receptors with weak antagonistic effect on the ETA1 receptor.
authors.affiliation: Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Karaki
authors.forename: S A
authors.initials: SA
authors.lastname: Sudjarwo
authors.forename: M
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D065128:Endothelin Receptor Antagonists; D007421:Intestine, Small / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation; D009842:Oligopeptides / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
chemical_list: D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; D010880:Piperidines; C086539:BQ 788