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![]() | |
2010-11-01 | |
Source Publication | British Journal of Pharmacology
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ISSN | 00071188 14765381 |
Volume | 161Issue: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. |
Keyword | 5-hydroxytryptamine Basilar Artery Mitochondrial Reactive Oxygen Species Monoamine Oxidases Spontaneously Hypertensive Rats |
DOI | 10.1111/j.1476-5381.2010.00941.x |
URL | View the original |
Indexed By | SCI |
WOS Research Area | Pharmacology & Pharmacy |
WOS Subject | Pharmacology & Pharmacy |
WOS ID | WOS:000282687900012 |
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Citation statistics | |
Document Type | Journal article |
Collection | Institute of Chinese Medical Sciences |
Affiliation | 1.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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