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Synergistic inhibition by BQ‐123 and BQ‐788 of endothelin‐1‐induced contractions of the rabbit pulmonary artery
Author(s) -
Fukuroda Takahiro,
Ozaki Satoshi,
Ihara Masaki,
Ishikawa Kiyofumi,
Yano Mitsuo,
Nishikibe Masaru
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb16901.x
Subject(s) - contraction (grammar) , endothelin receptor , antagonist , chemistry , vasoconstriction , agonist , receptor , endothelin 1 , hypoxic pulmonary vasoconstriction , pulmonary artery , medicine , endocrinology , receptor antagonist , pharmacology , biology , biochemistry
In the rabbit isolated pulmonary artery, neither the ET A receptor antagonist, BQ‐123 (10 μ m ), nor the ET B receptor antagonist, BQ‐788 (10 μ m ), inhibited the contractions induced by 1 n m endothelin‐1 (ET‐1). However, the combination of BQ‐123 and BQ‐788 completely inhibited the ET‐1‐induced contraction. In contrast, the ET B ‐selective agonist, sarafotoxin S6c (1 n m )‐induced contraction was completely inhibited by BQ‐788 but not by BQ‐123. In receptor binding assays, [ 125 I]‐ET‐1 specific binding to pulmonary arterial membranes was inhibited by BQ‐123 (1 μ m ) by approximately 20% and additive treatment with BQ‐788 (1 μ m ) completely inhibited the BQ‐123‐resistant component of [ 125 I]‐ET‐1 specific binding. The present study demonstrates synergistic inhibition by BQ‐123 and BQ‐788 of ET‐1‐induced contraction of the rabbit pulmonary artery and the coexistence of ET A and ET B receptors, suggesting that the activation of either only ET A or only ET B receptors may be sufficient to cause complete vasoconstriction. Therefore, blockade of both receptor subtypes would be necessary for the inhibition of some ET A /ET B composite types of responses.