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Article: Mitochondrial monoamine oxidase-A-mediated hydrogen peroxide generation enhances 5-hydroxytryptamine-induced contraction of rat basilar artery

TitleMitochondrial monoamine oxidase-A-mediated hydrogen peroxide generation enhances 5-hydroxytryptamine-induced contraction of rat basilar artery
Authors
Keywords5-hydroxytryptamine
Basilar artery
Mitochondrial reactive oxygen species
Monoamine oxidases
Spontaneously hypertensive rats
Issue Date2010
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
Citation
British Journal Of Pharmacology, 2010, v. 161 n. 5, p. 1086-1098 How to Cite?
AbstractBACKGROUND AND PURPOSE We evaluated the role(s) of monoamine oxidase (MAO)-mediated H 2O 2 generation on 5-hydroxytryptamine (5-HT)-induced tension development of isolated basilar artery of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. EXPERIMENTAL APPROACH Basilar artery (endothelium-denuded) was isolated for tension measurement and Western blots. Enzymically dissociated single myocytes from basilar arteries were used for patch-clamp electrophysiological and confocal microscopic studies. KEY RESULTS Under resting tension, 5-HT elicited a concentration-dependent tension development with a greater sensitivity (with unchanged maximum tension development) in SHR compared with WKY (EC 50: 28.4 ± 4.1-nM vs. 98.2 ± 9.4-nM). The exaggerated component of 5-HT-induced tension development in SHR was eradicated by polyethylene glycol-catalase, clorgyline and citalopram whereas exogenously applied H 2O 2 enhanced the 5-HT-elicited tension development in WKY. A greater protein expression of MAO-A was detected in basilar arteries from SHR than in those from WKY. In single myocytes and the entire basilar artery, 5-HT generated (clorgyline-sensitive) a greater amount of H 2O 2 in SHR compared with WKY. Whole-cell iberiotoxin-sensitive Ca 2+-activated K + (BK Ca) amplitude measured in myocytes of SHR was approximately threefold greater than that in WKY (at +60-mV: 7.61 ± 0.89-pA.pF -1 vs. 2.61 ± 0.66-pA.pF -1). In SHR myocytes, 5-HT caused a greater inhibition (clorgyline-, polyethylene glycol-catalase- and reduced glutathione-sensitive) of BK Ca amplitude than in those from WKY. CONCLUSIONS AND IMPLICATIONS 5-HT caused an increased generation of mitochondrial H 2O 2 via MAO-A-mediated 5-HT metabolism, which caused a greater inhibition of BK Ca gating in basilar artery myocytes, leading to exaggerated basilar artery tension development in SHR. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.
Persistent Identifierhttp://hdl.handle.net/10722/137487
ISSN
2014 Impact Factor: 4.842
2014 SCImago Journal Rankings: 1.844
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Li Ka Shing Institute of Health Sciences
Institute of Vascular Medicine (Faculty of Medicine, The Chinese University of Hong Kong)
UGC of Hong Kong4107/01M
4166/02M
2140565
Chinese University of Hong Kong2401149
2041231
2401296
Department of Pharmacology/School of Biomedical Sciences (The Chinese University of Hong Kong, Hong Kong)
Chou's Foundation
Funding Information:

We are grateful to Li Ka Shing Institute of Health Sciences and Institute of Vascular Medicine (Faculty of Medicine, The Chinese University of Hong Kong) for financial supports (to YW Kwan). This project is financially supported by UGC Earmarked Grants of Hong Kong (Ref. #: 4107/01M; 4166/02M, project code: 2140565) and Direct Grants for Research (The Chinese University of Hong Kong) (Reference no. 2401149; Project code/ID: 2041231; 2401296). Ms CCW Poon, Mr SW Seto, Ms ALS Au, Ms Q Zhang and Mr WYW Lee are recipients of postgraduate studentship of the Department of Pharmacology/School of Biomedical Sciences (The Chinese University of Hong Kong, Hong Kong). Provision of the Student Campus Work Scheme by the Chou's Foundation Fund and the Student Campus Work Scheme (Shaw College, The Chinese University of Hong Kong) is appreciated. Proofreading of the manuscript by Dr Ho Yeung Lam is acknowledged.

References

 

DC FieldValueLanguage
dc.contributor.authorPoon, CCWen_HK
dc.contributor.authorSeto, SWen_HK
dc.contributor.authorAu, ALSen_HK
dc.contributor.authorZhang, Qen_HK
dc.contributor.authorLi, RWSen_HK
dc.contributor.authorLee, WYWen_HK
dc.contributor.authorLeung, GPHen_HK
dc.contributor.authorKong, SKen_HK
dc.contributor.authorYeung, JHKen_HK
dc.contributor.authorNgai, SMen_HK
dc.contributor.authorHo, HPen_HK
dc.contributor.authorLee, SMYen_HK
dc.contributor.authorChan, SWen_HK
dc.contributor.authorKwan, YWen_HK
dc.date.accessioned2011-08-26T14:26:06Z-
dc.date.available2011-08-26T14:26:06Z-
dc.date.issued2010en_HK
dc.identifier.citationBritish Journal Of Pharmacology, 2010, v. 161 n. 5, p. 1086-1098en_HK
dc.identifier.issn0007-1188en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137487-
dc.description.abstractBACKGROUND AND PURPOSE We evaluated the role(s) of monoamine oxidase (MAO)-mediated H 2O 2 generation on 5-hydroxytryptamine (5-HT)-induced tension development of isolated basilar artery of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. EXPERIMENTAL APPROACH Basilar artery (endothelium-denuded) was isolated for tension measurement and Western blots. Enzymically dissociated single myocytes from basilar arteries were used for patch-clamp electrophysiological and confocal microscopic studies. KEY RESULTS Under resting tension, 5-HT elicited a concentration-dependent tension development with a greater sensitivity (with unchanged maximum tension development) in SHR compared with WKY (EC 50: 28.4 ± 4.1-nM vs. 98.2 ± 9.4-nM). The exaggerated component of 5-HT-induced tension development in SHR was eradicated by polyethylene glycol-catalase, clorgyline and citalopram whereas exogenously applied H 2O 2 enhanced the 5-HT-elicited tension development in WKY. A greater protein expression of MAO-A was detected in basilar arteries from SHR than in those from WKY. In single myocytes and the entire basilar artery, 5-HT generated (clorgyline-sensitive) a greater amount of H 2O 2 in SHR compared with WKY. Whole-cell iberiotoxin-sensitive Ca 2+-activated K + (BK Ca) amplitude measured in myocytes of SHR was approximately threefold greater than that in WKY (at +60-mV: 7.61 ± 0.89-pA.pF -1 vs. 2.61 ± 0.66-pA.pF -1). In SHR myocytes, 5-HT caused a greater inhibition (clorgyline-, polyethylene glycol-catalase- and reduced glutathione-sensitive) of BK Ca amplitude than in those from WKY. CONCLUSIONS AND IMPLICATIONS 5-HT caused an increased generation of mitochondrial H 2O 2 via MAO-A-mediated 5-HT metabolism, which caused a greater inhibition of BK Ca gating in basilar artery myocytes, leading to exaggerated basilar artery tension development in SHR. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1en_HK
dc.relation.ispartofBritish Journal of Pharmacologyen_HK
dc.rightsBritish Journal of Pharmacology. Copyright © John Wiley & Sons Ltd.-
dc.subject5-hydroxytryptamineen_HK
dc.subjectBasilar arteryen_HK
dc.subjectMitochondrial reactive oxygen speciesen_HK
dc.subjectMonoamine oxidasesen_HK
dc.subjectSpontaneously hypertensive ratsen_HK
dc.subject.meshHydrogen Peroxide - metabolism-
dc.subject.meshHypertension - physiopathology-
dc.subject.meshMitochondria - drug effects - metabolism-
dc.subject.meshMonoamine Oxidase - metabolism-
dc.subject.meshSerotonin - administration and dosage - pharmacology-
dc.titleMitochondrial monoamine oxidase-A-mediated hydrogen peroxide generation enhances 5-hydroxytryptamine-induced contraction of rat basilar arteryen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, GPH: gphleung@hkucc.hku.hken_HK
dc.identifier.authorityLeung, GPH=rp00234en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/j.1476-5381.2010.00941.xen_HK
dc.identifier.pmid20977458en_HK
dc.identifier.pmcidPMC2998689-
dc.identifier.scopuseid_2-s2.0-77958586636en_HK
dc.identifier.hkuros189210en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77958586636&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume161en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1086en_HK
dc.identifier.epage1098en_HK
dc.identifier.isiWOS:000282687900012-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridPoon, CCW=26656895800en_HK
dc.identifier.scopusauthoridSeto, SW=9941482400en_HK
dc.identifier.scopusauthoridAu, ALS=7005391144en_HK
dc.identifier.scopusauthoridZhang, Q=36674413300en_HK
dc.identifier.scopusauthoridLi, RWS=7404722884en_HK
dc.identifier.scopusauthoridLee, WYW=23035345800en_HK
dc.identifier.scopusauthoridLeung, GPH=35963668200en_HK
dc.identifier.scopusauthoridKong, SK=7203043875en_HK
dc.identifier.scopusauthoridYeung, JHK=7006803824en_HK
dc.identifier.scopusauthoridNgai, SM=7006074219en_HK
dc.identifier.scopusauthoridHo, HP=7401465498en_HK
dc.identifier.scopusauthoridLee, SMY=35233892600en_HK
dc.identifier.scopusauthoridChan, SW=7404255670en_HK
dc.identifier.scopusauthoridKwan, YW=7005662153en_HK

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