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学科主题: 基础医学
题名:
Emerging concepts and therapeutic implications of beta-adrenergic receptor subtype signaling
作者: Zheng, M; Zhu, WZ; Han, QD; Xiao, RP
关键词: G protein-coupled receptors ; beta-adrenergic receptor subtypes ; beta-adrenergic receptor polymorphisin ; G proteins ; PKA ; CaMKII PI3K ; apoptosis ; hypertrophy ; congestive heart failure ; beta-blocker therapy
刊名: PHARMACOLOGY & THERAPEUTICS
发表日期: 2005-12-01
DOI: 10.1016/j.pharmthera.2005.04.006
卷: 108, 期:3, 页:257-268
收录类别: SCI
文章类型: Review
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: CHRONIC HEART-FAILURE ; RAT VENTRICULAR MYOCYTES ; IDIOPATHIC DILATED CARDIOMYOPATHY ; PROTEIN-KINASE-A ; HUMAN BETA(1)-ADRENERGIC RECEPTOR ; RANDOMIZED INTERVENTION TRIAL ; FAILING HUMAN HEART ; N-TERMINAL KINASES ; BETA(2)-ADRENERGIC RECEPTOR ; CARDIAC MYOCYTES
英文摘要:

The stimulation of beta-adrenergic receptor (beta AR) plays a pivotal role in regulating myocardial function and morphology in the normal and failing heart. Three genetically and pharmacologically distinct beta AR subtypes, beta(1)AR, beta(2)AR, and beta(3)AR, are identified in various types of cells. While both beta(1)AR and beta(2)AR, the predominant beta AR subtypes expressed in the heart of many mammalian species including human, are Coupled to the G(s)-adenylyl cyclase-cAMP-PKA pathway, beta(2)AR dually activates pertussis toxin-sensitive G(i) proteins. During acute stimulation, beta(2)AR-G(i) coupling partially inhibits the G(s)-mediated positive contractile and relaxant effects via a G(i)-G(beta gamma)-phosphoinositide 3-kinase (PI3K)-dependent mechanism in adult rodent cardiomyocytes. More importantly, persistent beta(1)AR stimulation evokes a multitude of cardiac toxic effects, including myocyte apoptosis and hypertrophy, via a calmodulin-dependent protein kinase II (CaMKII)-, rather than cAMP-PKA-, dependent mechanism in rodent heart in vivo and cultured cardiomyocytes. In contrast, persistent beta(2)AR activation protects myocardium by a cell Survival pathway involving G(i), PI3K, and Akt. In this review, we attempt to highlight the distinct functionalities and signaling mechanisms of these beta AR subtypes and discuss how these subtype-specific properties of beta ARs might affect tile pathogenesis of congestive heart failure (CHF) and tile therapeutic effectiveness of certain beta-blockers in tile treatment of congestive heart failure. (c) 2005 Published by Elsevier Inc.

语种: 英语
WOS记录号: WOS:000233996900002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61106
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA
2.Peking Univ, Inst Cardiovasc Sci, Beijing 100083, Peoples R China
3.Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China

Recommended Citation:
Zheng, M,Zhu, WZ,Han, QD,et al. Emerging concepts and therapeutic implications of beta-adrenergic receptor subtype signaling[J]. PHARMACOLOGY & THERAPEUTICS,2005,108(3):257-268.
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