Inhibitory effects of brefeldin A, a membrane transport blocker, on the bradykinin‐induced hyperpolarization‐mediated relaxation in the porcine coronary artery
Y Ohnishi, K Hirano, J Nishimura… - British journal of …, 2001 - Wiley Online Library
British journal of pharmacology, 2001•Wiley Online Library
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 Ca2+ concentration ([Ca2+] i) and tension was determined in the porcine coronary
arterial strips. We also examined the effect of brefeldin A on [Ca2+] i in the endothelial cells
of the porcine aortic valve. In the presence of 10 μm indomethacin and 30 μm NG‐nitro‐l‐
arginine (l‐NOARG), both bradykinin and substance P induced a transient decrease in …
hyperpolarizing factors (EDHFs), the effect of brefeldin A, a membrane transport blocker, on
cytosolic Ca2+ concentration ([Ca2+] i) and tension was determined in the porcine coronary
arterial strips. We also examined the effect of brefeldin A on [Ca2+] i in the endothelial cells
of the porcine aortic valve. In the presence of 10 μm indomethacin and 30 μm NG‐nitro‐l‐
arginine (l‐NOARG), both bradykinin and substance P induced a transient decrease in …
- 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 Ca2+ concentration ([Ca2+]i) and tension was determined in the porcine coronary arterial strips. We also examined the effect of brefeldin A on [Ca2+]i in the endothelial cells of the porcine aortic valve.
- In the presence of 10 μM indomethacin and 30 μM NG‐nitro‐L‐arginine (L‐NOARG), both bradykinin and substance P induced a transient decrease in [Ca2+]i and tension in arterial strips contracted with 100 nM U46619 (thromboxane A2 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 mM K+.
- The indomethacin/L‐NOARG‐resistant relaxation induced by bradykinin was completely inhibited by 3 mM tetrabutylammonium (non‐specific Ca2+‐activated K+ channel blocker), while that induced by substance P was not inhibited by 3 mM tetrabutylammonium or 1 mM 4‐aminopyridine (voltage‐dependent K+ channels blocker) alone, but completely inhibited by their combination.
- Brefeldin A had no effect on the [Ca2+]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
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