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Mitochondrial monoamine oxidase-A-mediated hydrogen peroxide generation enhances 5-hydroxytryptamine-induced contraction of rat basilar artery
Poon C.C.W.1; Seto S.W.1; Au A.L.S.1; Zhang Q.1; Li R.W.S.4; Lee W.Y.W.1; Leung G.P.H.4; Kong S.K.1; Yeung J.H.K.1; Ngai S.M.1; Ho H.P.1; Lee S.M.Y.5; Chan S.W.3; Kwan Y.W.1
2010-11-01
Source PublicationBritish Journal of Pharmacology
ISSN00071188 14765381
Volume161Issue:5Pages:1086-1098
Abstract

BACKGROUND AND PURPOSE We evaluated the role(s) of monoamine oxidase (MAO)-mediated H O 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 : 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 O 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 O in SHR compared with WKY. Whole-cell iberiotoxin-sensitive Ca -activated K (BK ) amplitude measured in myocytes of SHR was approximately threefold greater than that in WKY (at +60-mV: 7.61 ± 0.89-pA.pF vs. 2.61 ± 0.66-pA.pF ). In SHR myocytes, 5-HT caused a greater inhibition (clorgyline-, polyethylene glycol-catalase- and reduced glutathione-sensitive) of BK amplitude than in those from WKY. CONCLUSIONS AND IMPLICATIONS 5-HT caused an increased generation of mitochondrial H O via MAO-A-mediated 5-HT metabolism, which caused a greater inhibition of BK 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.

Keyword5-hydroxytryptamine Basilar Artery Mitochondrial Reactive Oxygen Species Monoamine Oxidases Spontaneously Hypertensive Rats
DOI10.1111/j.1476-5381.2010.00941.x
URLView the original
Indexed BySCI
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000282687900012
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Cited Times [WOS]:17   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Chinese University of Hong Kong
2.State Key Laboratory of Chinese Medicine and Molecular Pharmacology
3.Hong Kong Polytechnic University
4.The University of Hong Kong
5.University of Macau
Recommended Citation
GB/T 7714
Poon C.C.W.,Seto S.W.,Au A.L.S.,et al. Mitochondrial monoamine oxidase-A-mediated hydrogen peroxide generation enhances 5-hydroxytryptamine-induced contraction of rat basilar artery[J]. British Journal of Pharmacology,2010,161(5):1086-1098.
APA Poon C.C.W..,Seto S.W..,Au A.L.S..,Zhang Q..,Li R.W.S..,...&Kwan Y.W..(2010).Mitochondrial monoamine oxidase-A-mediated hydrogen peroxide generation enhances 5-hydroxytryptamine-induced contraction of rat basilar artery.British Journal of Pharmacology,161(5),1086-1098.
MLA Poon C.C.W.,et al."Mitochondrial monoamine oxidase-A-mediated hydrogen peroxide generation enhances 5-hydroxytryptamine-induced contraction of rat basilar artery".British Journal of Pharmacology 161.5(2010):1086-1098.
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