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Distinct #beta#-adrenergic receptor subtype signaling in the heart and their pathophysiological relevance

Zheng Ming, Han Qide, Xiao Ruiping

The Institute of Molecular Medicine,Peking University.Beijing 100083

Abstract

As a result, acute #beta#_(1)AR stimulation activates the G_(s)-adenylyl cyclase-cAMP-PKA signaling that can broadcast throughout the cell, whereas #beta#_(2)AR-evoked cAMP signaling is spatially and functionally compartmentalized, due to concurrent G_(i) activation. Chronic stimulation of #beta#_(1)AR and #beta#_(2)AR elicits opposing effects on the fate of cardiomyocytes: #beta#_(1)AR induces hypertrophy and apoptosis; but #beta#_(2)AR promotes cell survival. The cardiac protective effect of #beta#_(2)AR is mediated by a signaling pathway sequentially involving G_(i), G_(#beta##gamma#), PI3K and Akt. Unexpectedly, #beta#_(1)AR-induced myocyte hypertrophy and apoptosis are independent of the classic cAMP/PKA pathway, but require activation of Ca~(2+)/calmodulin-dependent kinase II (CaMK II). The outcomes of cardiac-specifici transgenic overexpression of either #beta#AR subtype in mice have reinforced the fundamentally different functional roles of these #beta#AR subtypes in governing cardiac remodeling and performance. These new insights regarding #beta#AR subtype stimulation not only provide clues as to cellular and molecular mechanisms underlying the beneficial effects of #beta#AR blockers in patients with chronic heart failure, but also delineate rationale for combining selective #beta#_(1)AR blockade with moderate #beta#_(2)AR activation as a potential novel therapy for the treatment of chronic heart failure.

Key words: β肾上腺素受体;心脏;信号传导

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Citing This Article：

Zheng Ming, Han Qide, Xiao Ruiping. Distinct #beta#-adrenergic receptor subtype signaling in the heart and their pathophysiological relevance. Acta Physiol Sin 2004; 56 (1): (in Chinese with English abstract).