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Article: 14,15-Epoxyeicosatrienoic acid induces vasorelaxation through the prostaglandin EP2 receptors in rat mesenteric artery

Title14,15-Epoxyeicosatrienoic acid induces vasorelaxation through the prostaglandin EP2 receptors in rat mesenteric artery
Authors
KeywordsEETs
Prostanoid
Vascular smooth muscle cells
Vasorelaxation
Issue Date2010
PublisherElsevier 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?
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 (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.
Persistent Identifierhttp://hdl.handle.net/10722/137485
ISSN
2023 Impact Factor: 2.5
2023 SCImago Journal Rankings: 0.671
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong SAR769607
University of Hong Kong200711159031
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).

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DC FieldValueLanguage
dc.contributor.authorYang, Cen_HK
dc.contributor.authorKwan, YWen_HK
dc.contributor.authorAu, ALSen_HK
dc.contributor.authorPoon, CCWen_HK
dc.contributor.authorZhang, Qen_HK
dc.contributor.authorChan, SWen_HK
dc.contributor.authorLee, SMYen_HK
dc.contributor.authorLeung, GPHen_HK
dc.date.accessioned2011-08-26T14:26:04Z-
dc.date.available2011-08-26T14:26:04Z-
dc.date.issued2010en_HK
dc.identifier.citationProstaglandins And Other Lipid Mediators, 2010, v. 93 n. 1-2, p. 44-51en_HK
dc.identifier.issn1098-8823en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137485-
dc.description.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 (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.en_HK
dc.languageengen_US
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/prostaglandinsen_HK
dc.relation.ispartofProstaglandins and Other Lipid Mediatorsen_HK
dc.subjectEETsen_HK
dc.subjectProstanoiden_HK
dc.subjectVascular smooth muscle cellsen_HK
dc.subjectVasorelaxationen_HK
dc.subject.mesh8,11,14-Eicosatrienoic Acid - analogs and derivatives - pharmacology-
dc.subject.meshMesenteric Arteries - drug effects - metabolism - physiology-
dc.subject.meshReceptors, Prostaglandin E, EP2 Subtype - metabolism-
dc.subject.meshVasodilation - drug effects-
dc.subject.meshVasodilator Agents - pharmacology-
dc.title14,15-Epoxyeicosatrienoic acid induces vasorelaxation through the prostaglandin EP2 receptors in rat mesenteric arteryen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, GPH: gphleung@hkucc.hku.hken_HK
dc.identifier.authorityLeung, GPH=rp00234en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.prostaglandins.2010.06.004en_HK
dc.identifier.pmid20601071-
dc.identifier.scopuseid_2-s2.0-77955421347en_HK
dc.identifier.hkuros189173en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77955421347&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume93en_HK
dc.identifier.issue1-2en_HK
dc.identifier.spage44en_HK
dc.identifier.epage51en_HK
dc.identifier.isiWOS:000281748000008-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectFunction and regulation of cystic fibrosis transmembrane conductance regulator (CFTR) in endothelail cells-
dc.identifier.scopusauthoridYang, C=7407028637en_HK
dc.identifier.scopusauthoridKwan, YW=7005662153en_HK
dc.identifier.scopusauthoridAu, ALS=7005391144en_HK
dc.identifier.scopusauthoridPoon, CCW=26656895800en_HK
dc.identifier.scopusauthoridZhang, Q=20735917800en_HK
dc.identifier.scopusauthoridChan, SW=7404255670en_HK
dc.identifier.scopusauthoridLee, SMY=35233892600en_HK
dc.identifier.scopusauthoridLeung, GPH=35963668200en_HK
dc.identifier.issnl1098-8823-

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