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Article: Inhibitory effects of epoxyeicosatrienoic acids on volume-activated chloride channels in rat mesenteric arterial smooth muscle

TitleInhibitory effects of epoxyeicosatrienoic acids on volume-activated chloride channels in rat mesenteric arterial smooth muscle
Authors
KeywordsChloride channels
Cyclic GMP
Epoxyeicosatrienoic acids
Mesenteric arteries
Smooth muscle
Issue Date2008
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/prostaglandins
Citation
Prostaglandins And Other Lipid Mediators, 2008, v. 87 n. 1-4, p. 62-67 How to Cite?
AbstractEpoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by cytochrome P450 epoxygenases in endothelial cells. It has previously been shown that EETs activate K+ channels, which are important for the hyperpolarization and dilation of blood vessels. However, the effects of EETs on other ion channels have been less well studied. We investigated the effects of EETs on volume-activated Cl- channels (VACCs) in rat mesenteric arterial smooth muscle cells. Whole-cell patch clamp recording demonstrated that hypotonic solution and guanosine 5′-[γ-thio]triphosphate (GTPγS) induced a 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB)- and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS)-sensitive VACC current in the primary cultured rat mesenteric arterial smooth muscle cells. The VACC current was inhibited by EETs and the order of potency was 8,9-EET > 5,6-EET > 11,12-EET > 14,15-EET. The inhibitory effects of EETs could be reversed by 14,15 epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, an EET analog), Rp-cGMP and KT-5823 (protein kinase G inhibitors). Interestingly, the inhibitory effects of EETs on VACCs were not influenced by Rp-cAMP (a protein kinase A antagonist) but it could be abolished by NF-449 (a Gs protein inhibitor), indicating the involvement of cAMP but not protein kinase A. In conclusion, our results demonstrate that EETs inhibit VACCs in rat mesenteric arterial smooth muscle cells through a cGMP-dependent pathway, which is probably due to the cross-activation by cAMP. This mechanism may be involved in the regulation of cell volume and membrane potential. © 2008 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/59540
ISSN
2015 Impact Factor: 2.905
2015 SCImago Journal Rankings: 1.142
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong SAR769607
University of Hong Kong
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.

References

 

DC FieldValueLanguage
dc.contributor.authorYang, Cen_HK
dc.contributor.authorKwan, YWen_HK
dc.contributor.authorSeto, SWen_HK
dc.contributor.authorLeung, GPHen_HK
dc.date.accessioned2010-05-31T03:52:20Z-
dc.date.available2010-05-31T03:52:20Z-
dc.date.issued2008en_HK
dc.identifier.citationProstaglandins And Other Lipid Mediators, 2008, v. 87 n. 1-4, p. 62-67en_HK
dc.identifier.issn1098-8823en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59540-
dc.description.abstractEpoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by cytochrome P450 epoxygenases in endothelial cells. It has previously been shown that EETs activate K+ channels, which are important for the hyperpolarization and dilation of blood vessels. However, the effects of EETs on other ion channels have been less well studied. We investigated the effects of EETs on volume-activated Cl- channels (VACCs) in rat mesenteric arterial smooth muscle cells. Whole-cell patch clamp recording demonstrated that hypotonic solution and guanosine 5′-[γ-thio]triphosphate (GTPγS) induced a 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB)- and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS)-sensitive VACC current in the primary cultured rat mesenteric arterial smooth muscle cells. The VACC current was inhibited by EETs and the order of potency was 8,9-EET > 5,6-EET > 11,12-EET > 14,15-EET. The inhibitory effects of EETs could be reversed by 14,15 epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, an EET analog), Rp-cGMP and KT-5823 (protein kinase G inhibitors). Interestingly, the inhibitory effects of EETs on VACCs were not influenced by Rp-cAMP (a protein kinase A antagonist) but it could be abolished by NF-449 (a Gs protein inhibitor), indicating the involvement of cAMP but not protein kinase A. In conclusion, our results demonstrate that EETs inhibit VACCs in rat mesenteric arterial smooth muscle cells through a cGMP-dependent pathway, which is probably due to the cross-activation by cAMP. This mechanism may be involved in the regulation of cell volume and membrane potential. © 2008 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
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.subjectChloride channelsen_HK
dc.subjectCyclic GMPen_HK
dc.subjectEpoxyeicosatrienoic acidsen_HK
dc.subjectMesenteric arteriesen_HK
dc.subjectSmooth muscleen_HK
dc.titleInhibitory effects of epoxyeicosatrienoic acids on volume-activated chloride channels in rat mesenteric arterial smooth muscleen_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.2008.08.003en_HK
dc.identifier.pmid18812234-
dc.identifier.scopuseid_2-s2.0-55549148717en_HK
dc.identifier.hkuros157512en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-55549148717&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume87en_HK
dc.identifier.issue1-4en_HK
dc.identifier.spage62en_HK
dc.identifier.epage67en_HK
dc.identifier.isiWOS:000261662700010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridYang, C=7407028637en_HK
dc.identifier.scopusauthoridKwan, YW=7005662153en_HK
dc.identifier.scopusauthoridSeto, SW=9941482400en_HK
dc.identifier.scopusauthoridLeung, GPH=35963668200en_HK

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