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Inhibitory effects of brefeldin A, a membrane transport blocker, on the bradykinin‐induced hyperpolarization‐mediated relaxation in the porcine coronary artery
Author(s) -
Ohnishi Yoshinori,
Hirano Katsuya,
Nishimura Junji,
Furue Masutaka,
Kanaide Hideo
Publication year - 2001
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 - 10.1038/sj.bjp.0704246
Subject(s) - bradykinin , brefeldin a , chemistry , thromboxane a2 , endothelium derived hyperpolarizing factor , apamin , channel blocker , prostacyclin , pharmacology , medicine , hyperpolarization (physics) , contraction (grammar) , cromakalim , potassium channel , endocrinology , glibenclamide , membrane potential , biochemistry , resting potential , calcium , stereochemistry , endoplasmic reticulum , receptor , nuclear magnetic resonance spectroscopy , golgi apparatus , diabetes mellitus
To elucidate the mechanism of the relaxation mediated by endothelium‐derived hyperpolarizing factors (EDHFs), the effect of brefeldin A, a membrane transport blocker, on cytosolic Ca 2+ concentration ([Ca 2+ ] i ) and tension was determined in the porcine coronary arterial strips. We also examined the effect of brefeldin A on [Ca 2+ ] i in the endothelial cells of the porcine aortic valve. In the presence of 10 μ M indomethacin and 30 μ M N G ‐nitro‐ L ‐arginine ( L ‐NOARG), both bradykinin and substance P induced a transient decrease in [Ca 2+ ] i and tension in arterial strips contracted with 100 n M U46619 (thromboxane A 2 analogue). A 6 h pre‐treatment with 20 μg ml −1 brefeldin A abolished the bradykinin‐induced relaxation, while it had no effect on the substance P‐induced relaxation. In the absence of indomethacin and L ‐NOARG, brefeldin A had no effect on the bradykinin‐induced relaxation during the contraction induced by U46619 or 118 m M K + . The indomethacin/ L ‐NOARG‐resistant relaxation induced by bradykinin was completely inhibited by 3 m M tetrabutylammonium (non‐specific Ca 2+ ‐activated K + channel blocker), while that induced by substance P was not inhibited by 3 m M tetrabutylammonium or 1 m M 4‐aminopyridine (voltage‐dependent K + channels blocker) alone, but completely inhibited by their combination. Brefeldin A had no effect on the [Ca 2+ ] i elevation in endothelial cells induced by bradykinin or substance P. In conclusion, bradykinin produce EDHF in a brefeldin A‐sensitive mechanism in the porcine coronary artery. However, this mechanism is not active in a substance P‐induced production of EDHF, which thus suggests EDHF to be more than a single entity.British Journal of Pharmacology (2001) 134 , 168–178; doi: 10.1038/sj.bjp.0704246