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- Publisher Website: 10.1016/j.prostaglandins.2008.08.003
- Scopus: eid_2-s2.0-55549148717
- PMID: 18812234
- WOS: WOS:000261662700010
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Article: Inhibitory effects of epoxyeicosatrienoic acids on volume-activated chloride channels in rat mesenteric arterial smooth muscle
Title | Inhibitory effects of epoxyeicosatrienoic acids on volume-activated chloride channels in rat mesenteric arterial smooth muscle | ||||||
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Authors | |||||||
Keywords | Chloride channels Cyclic GMP Epoxyeicosatrienoic acids Mesenteric arteries Smooth muscle | ||||||
Issue Date | 2008 | ||||||
Publisher | Elsevier 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? | ||||||
Abstract | Epoxyeicosatrienoic 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 Identifier | http://hdl.handle.net/10722/59540 | ||||||
ISSN | 2023 Impact Factor: 2.5 2023 SCImago Journal Rankings: 0.671 | ||||||
ISI Accession Number ID |
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 Field | Value | Language |
---|---|---|
dc.contributor.author | Yang, C | en_HK |
dc.contributor.author | Kwan, YW | en_HK |
dc.contributor.author | Seto, SW | en_HK |
dc.contributor.author | Leung, GPH | en_HK |
dc.date.accessioned | 2010-05-31T03:52:20Z | - |
dc.date.available | 2010-05-31T03:52:20Z | - |
dc.date.issued | 2008 | en_HK |
dc.identifier.citation | Prostaglandins And Other Lipid Mediators, 2008, v. 87 n. 1-4, p. 62-67 | en_HK |
dc.identifier.issn | 1098-8823 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/59540 | - |
dc.description.abstract | Epoxyeicosatrienoic 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.language | eng | en_HK |
dc.publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/prostaglandins | en_HK |
dc.relation.ispartof | Prostaglandins and Other Lipid Mediators | en_HK |
dc.subject | Chloride channels | en_HK |
dc.subject | Cyclic GMP | en_HK |
dc.subject | Epoxyeicosatrienoic acids | en_HK |
dc.subject | Mesenteric arteries | en_HK |
dc.subject | Smooth muscle | en_HK |
dc.title | Inhibitory effects of epoxyeicosatrienoic acids on volume-activated chloride channels in rat mesenteric arterial smooth muscle | en_HK |
dc.type | Article | en_HK |
dc.identifier.email | Leung, GPH: gphleung@hkucc.hku.hk | en_HK |
dc.identifier.authority | Leung, GPH=rp00234 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.prostaglandins.2008.08.003 | en_HK |
dc.identifier.pmid | 18812234 | - |
dc.identifier.scopus | eid_2-s2.0-55549148717 | en_HK |
dc.identifier.hkuros | 157512 | en_HK |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-55549148717&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 87 | en_HK |
dc.identifier.issue | 1-4 | en_HK |
dc.identifier.spage | 62 | en_HK |
dc.identifier.epage | 67 | en_HK |
dc.identifier.isi | WOS:000261662700010 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.scopusauthorid | Yang, C=7407028637 | en_HK |
dc.identifier.scopusauthorid | Kwan, YW=7005662153 | en_HK |
dc.identifier.scopusauthorid | Seto, SW=9941482400 | en_HK |
dc.identifier.scopusauthorid | Leung, GPH=35963668200 | en_HK |
dc.identifier.issnl | 1098-8823 | - |