14,15-Epoxyeicosatrienoic acid induces vasorelaxation through the prostaglandin EP2 receptors in rat mesenteric artery
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AbstractEpoxyeicosatrienoic acids (EETs) induce vasorelaxation, probably through G protein-coupled receptors The identity of these receptors is unclear, but it has been reported that EETs may bind to peroxisome proliferator activated receptors (PPARs) and E-prostanoid (EP) receptors. Therefore, we studied whether PPARs or EP receptors were involved in 14,15-EET-induced vasorelaxation. Isometric tensions of rat mesenteric arteries were measured The vasorelaxant effect of 14,15-EET was inhibited by NF449 (G(s)-protein inhibitor), Rp-cAMP (cAMP antagonist) and KT5720 (PKA inhibitor), suggesting that the effect of 14,15-EET was mediated through G(s) protein-coupled receptors which were linked to the cAMP/PKA-dependent pathway Pretreatments with MK886 (PPAR(alpha) antagonist) and GW9662 (PPAR(gamma) antagonist) did not influence 14,15-EET-induced vasorelaxation. The vasorelaxant effect of 14,15-EET was inhibited by AH6809 (EP2 receptor antagonist), whereas SC19220 (EP1 receptor antagonist), L798106 (EP3 receptor antagonist) and GW627368X (EP4 receptor antagonist) had no effect The effect of 14,15-EET and the mechanism involved was mimicked by prostaglandin E-2 (an EP2 receptor agonist). The 14,15-EET-induced relaxation was slightly potentiated in the presence of indomethacin (cyclooxygenase inhibitor which block PGE(2) synthesis). Binding study showed that the amount of 14,15-EET bound to the cell membrane of rat mesenteric arterial smooth muscle cells was much higher than that bound to the nuclear membrane The binding of 14,15-EET to the cell membrane was attenuated by AH6809 and siRNA against EP2 receptors In conclusion, our study has demonstrated that 14,15-EET exerts relaxant effects on rat mesenteric arteries, at least partly via the stimulation of EP2 receptors This subsequently leads to activation of cAMP/PKA-dependent pathway in vascular smooth muscle cells (C) 2010 Elsevier Inc All rights reserved.
All Author(s) ListYang C, Kwan YW, Au ALS, Poon CCW, Zhang QA, Chan SW, Lee SMY, Leung GPH
Journal nameProstaglandins and Other Lipid Mediators
Detailed descriptionTo ORKTS: doi: 10.1016/j.prostaglandins.2010.06.004
Volume Number93
Issue Number1-2
Pages44 - 51
LanguagesEnglish-United Kingdom
KeywordsEETs; Prostanoid; Vascular smooth muscle cells; Vasorelaxation
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology; CELL BIOLOGY

Last updated on 2021-23-09 at 23:52