Article: 14,15-Epoxyeicosatrienoic acid induces vasorelaxation through the prostaglandin EP2 receptors in rat mesenteric artery
| Title | 14,15-Epoxyeicosatrienoic acid induces vasorelaxation through the prostaglandin EP2 receptors in rat mesenteric artery |
|---|---|
| Authors | Yang, C1 Kwan, YW4 Au, ALS4 Poon, CCW4 Zhang, Q4 Chan, SW3 Lee, SMY2 Leung, GPH1 |
| Keywords | EETs Prostanoid Vascular smooth muscle cells Vasorelaxation |
| Issue Date | 2010 |
| Publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/prostaglandins |
| Citation | Prostaglandins And Other Lipid Mediators, 2010, v. 93 n. 1-2, p. 44-51 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.prostaglandins.2010.06.004 |
| Abstract | Epoxyeicosatrienoic 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 (Gs-protein inhibitor), Rp-cAMP (cAMP antagonist) and KT5720 (PKA inhibitor), suggesting that the effect of 14,15-EET was mediated through Gs protein-coupled receptors which were linked to the cAMP/PKA-dependent pathway. Pretreatments with MK886 (PPARα antagonist) and GW9662 (PPARγ 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 E2 (an EP2 receptor agonist). The 14,15-EET-induced relaxation was slightly potentiated in the presence of indomethacin (cyclooxygenase inhibitor which block PGE2 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. © 2010 Elsevier Inc. |
| ISSN | 1098-8823 2011 Impact Factor: 2.705 2011 SCImago Journal Rankings: 0.190 |
| DOI | http://dx.doi.org/10.1016/j.prostaglandins.2010.06.004 |
| References | References in Scopus |
| Grants | Function and regulation of cystic fibrosis transmembrane conductance regulator (CFTR) in endothelail cells |
| dc.contributor.author | Yang, C | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Kwan, YW | ||||||
| dc.contributor.author | Au, ALS | ||||||
| dc.contributor.author | Poon, CCW | ||||||
| dc.contributor.author | Zhang, Q | ||||||
| dc.contributor.author | Chan, SW | ||||||
| dc.contributor.author | Lee, SMY | ||||||
| dc.contributor.author | Leung, GPH | ||||||
| dc.date.accessioned | 2011-08-26T14:26:04Z | ||||||
| dc.date.available | 2011-08-26T14:26:04Z | ||||||
| dc.date.issued | 2010 | ||||||
| dc.description.abstract | Epoxyeicosatrienoic 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 (Gs-protein inhibitor), Rp-cAMP (cAMP antagonist) and KT5720 (PKA inhibitor), suggesting that the effect of 14,15-EET was mediated through Gs protein-coupled receptors which were linked to the cAMP/PKA-dependent pathway. Pretreatments with MK886 (PPARα antagonist) and GW9662 (PPARγ 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 E2 (an EP2 receptor agonist). The 14,15-EET-induced relaxation was slightly potentiated in the presence of indomethacin (cyclooxygenase inhibitor which block PGE2 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. © 2010 Elsevier Inc. | ||||||
| dc.description.grant | Function and regulation of cystic fibrosis transmembrane conductance regulator (CFTR) in endothelail cells | ||||||
| dc.description.grantcode | 97868 | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Prostaglandins And Other Lipid Mediators, 2010, v. 93 n. 1-2, p. 44-51 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.prostaglandins.2010.06.004 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1016/j.prostaglandins.2010.06.004 | ||||||
| dc.identifier.epage | 51 | ||||||
| dc.identifier.hkuros | 189173 | ||||||
| dc.identifier.isi | WOS:000281748000008
Funding Information: This work was supported by the RGC Earmarked Grants of Hong Kong SAR (project code: 769607), and the Seed Funding for Basic Research Program of the University of Hong Kong (project code: 200711159031). | ||||||
| dc.identifier.issn | 1098-8823 2011 Impact Factor: 2.705 2011 SCImago Journal Rankings: 0.190 | ||||||
| dc.identifier.issue | 1-2 | ||||||
| dc.identifier.pmid | 20601071 | ||||||
| dc.identifier.scopus | eid_2-s2.0-77955421347 | ||||||
| dc.identifier.spage | 44 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/137485 | ||||||
| dc.identifier.volume | 93 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/prostaglandins | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Prostaglandins and Other Lipid Mediators | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject.mesh | 8,11,14-Eicosatrienoic Acid - analogs and derivatives - pharmacology | ||||||
| dc.subject.mesh | Mesenteric Arteries - drug effects - metabolism - physiology | ||||||
| dc.subject.mesh | Receptors, Prostaglandin E, EP2 Subtype - metabolism | ||||||
| dc.subject.mesh | Vasodilation - drug effects | ||||||
| dc.subject.mesh | Vasodilator Agents - pharmacology | ||||||
| dc.subject | EETs | ||||||
| dc.subject | Prostanoid | ||||||
| dc.subject | Vascular smooth muscle cells | ||||||
| dc.subject | Vasorelaxation | ||||||
| dc.title | 14,15-Epoxyeicosatrienoic acid induces vasorelaxation through the prostaglandin EP2 receptors in rat mesenteric artery | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- University of Macau
- Hong Kong Polytechnic University
- Chinese University of Hong Kong