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Article: Mitochondrial monoamine oxidase-A-mediated hydrogen peroxide generation enhances 5-hydroxytryptamine-induced contraction of rat basilar artery
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TitleMitochondrial monoamine oxidase-A-mediated hydrogen peroxide generation enhances 5-hydroxytryptamine-induced contraction of rat basilar artery
 
AuthorsPoon, CCW
Seto, SW
Au, ALS
Zhang, Q
Li, RWS1
Lee, WYW
Leung, GPH1
Kong, SK5
Yeung, JHK
Ngai, SM5
Ho, HP5
Lee, SMY2
Chan, SW4 3
Kwan, YW5
 
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
 
CitationBritish Journal Of Pharmacology, 2010, v. 161 n. 5, p. 1086-1098 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1476-5381.2010.00941.x
 
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.
 
ISSN0007-1188
2013 Impact Factor: 4.990
2013 SCImago Journal Rankings: 2.253
 
DOIhttp://dx.doi.org/10.1111/j.1476-5381.2010.00941.x
 
PubMed Central IDPMC2998689
 
ISI Accession Number IDWOS:000282687900012
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.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorPoon, CCW
 
dc.contributor.authorSeto, SW
 
dc.contributor.authorAu, ALS
 
dc.contributor.authorZhang, Q
 
dc.contributor.authorLi, RWS
 
dc.contributor.authorLee, WYW
 
dc.contributor.authorLeung, GPH
 
dc.contributor.authorKong, SK
 
dc.contributor.authorYeung, JHK
 
dc.contributor.authorNgai, SM
 
dc.contributor.authorHo, HP
 
dc.contributor.authorLee, SMY
 
dc.contributor.authorChan, SW
 
dc.contributor.authorKwan, YW
 
dc.date.accessioned2011-08-26T14:26:06Z
 
dc.date.available2011-08-26T14:26:06Z
 
dc.date.issued2010
 
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.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationBritish Journal Of Pharmacology, 2010, v. 161 n. 5, p. 1086-1098 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1476-5381.2010.00941.x
 
dc.identifier.doihttp://dx.doi.org/10.1111/j.1476-5381.2010.00941.x
 
dc.identifier.epage1098
 
dc.identifier.hkuros189210
 
dc.identifier.isiWOS:000282687900012
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.

 
dc.identifier.issn0007-1188
2013 Impact Factor: 4.990
2013 SCImago Journal Rankings: 2.253
 
dc.identifier.issue5
 
dc.identifier.pmcidPMC2998689
 
dc.identifier.pmid20977458
 
dc.identifier.scopuseid_2-s2.0-77958586636
 
dc.identifier.spage1086
 
dc.identifier.urihttp://hdl.handle.net/10722/137487
 
dc.identifier.volume161
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofBritish Journal of Pharmacology
 
dc.relation.referencesReferences in Scopus
 
dc.rightsBritish Journal of Pharmacology. Copyright © John Wiley & Sons Ltd.
 
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.subject5-hydroxytryptamine
 
dc.subjectBasilar artery
 
dc.subjectMitochondrial reactive oxygen species
 
dc.subjectMonoamine oxidases
 
dc.subjectSpontaneously hypertensive rats
 
dc.titleMitochondrial monoamine oxidase-A-mediated hydrogen peroxide generation enhances 5-hydroxytryptamine-induced contraction of rat basilar artery
 
dc.typeArticle
 
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<contributor.author>Seto, SW</contributor.author>
<contributor.author>Au, ALS</contributor.author>
<contributor.author>Zhang, Q</contributor.author>
<contributor.author>Li, RWS</contributor.author>
<contributor.author>Lee, WYW</contributor.author>
<contributor.author>Leung, GPH</contributor.author>
<contributor.author>Kong, SK</contributor.author>
<contributor.author>Yeung, JHK</contributor.author>
<contributor.author>Ngai, SM</contributor.author>
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<description.abstract>BACKGROUND 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 &#177; 4.1-nM vs. 98.2 &#177; 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 &#177; 0.89-pA.pF -1 vs. 2.61 &#177; 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. &#169; 2010 The Authors. British Journal of Pharmacology &#169; 2010 The British Pharmacological Society.</description.abstract>
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Author Affiliations
  1. The University of Hong Kong
  2. University of Macau
  3. State Key Laboratory of Chinese Medicine and Molecular Pharmacology
  4. Hong Kong Polytechnic University
  5. Chinese University of Hong Kong