Inhibitory effects of brefeldin A, a membrane transport blocker, on the bradykinin-induced hyperpolarization-mediated relaxation in the porcine coronary artery

Yoshinori Ohnishi, Katsuya Hirano, Junji Nishimura, Masutaka Furue, Hideo Kanaide

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

1 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. 2 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. 3 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+. 4 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 (voltagedependent K+ channels blocker) alone, but completely inhibited by their combination. 5 Brefeldin A had no effect on the [Ca2+]i elevation in endothelial cells induced by bradykinin or substance P. 6 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.

Original languageEnglish
Pages (from-to)168-178
Number of pages11
JournalBritish Journal of Pharmacology
Volume134
Issue number1
DOIs
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Pharmacology

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