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Sci. STKE, 16 October 2001
Vol. 2001, Issue 104, p. re15
[DOI: 10.1126/stke.2001.104.re15]

REVIEWS

ß-Adrenergic Signaling in the Heart: Dual Coupling of the ß2-Adrenergic Receptor to Gs and Gi Proteins

Rui-Ping Xiao

Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Baltimore, MD 21224, USA.

Contact information: Tel: 410 558-8662, Fax: 410 558-8150, E-mail: XiaoR{at}grc.nia.nih.gov

Abstract: ß-adrenergic receptor (AR) subtypes are archetypical members of the G protein-coupled receptor (GPCR) superfamily. Whereas both ß1AR and ß2AR stimulate the classic Gs-adenylyl cyclase-3',5'-adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling cascade, ß2AR couples to both Gs and Gi proteins, activating bifurcated signaling pathways. In the heart, dual coupling of the ß2AR to Gs and Gi results in compartmentalization of the Gs-stimulated cAMP signal, thus selectively affecting plasma membrane effectors (such as L-type Ca2+ channels) and bypassing cytoplasmic target proteins (such as phospholamban and myofilament contractile proteins). More important, the ß2AR-to-Gi branch delivers a powerful cell survival signal that counters apoptosis induced by the concurrent Gs-mediated signal or by a wide range of assaulting factors. This survival pathway sequentially involves Gi, Gß{gamma}, phosphoinositide 3-kinase, and Akt. Furthermore, cardiac-specific transgenic overexpression of ßAR subtypes in mice results in distinctly different phenotypes in terms of the likelihood of cardiac hypertrophy and heart failure. These findings indicate that stimulation of the two ßAR subtypes activates overlapping, but different, sets of signal transduction mechanisms, and fulfills distinct or even opposing physiological and pathophysiological roles. Because of these differences, selective activation of cardiac ß2AR may provide catecholamine-dependent inotropic support without cardiotoxic consequences, which might have beneficial effects in the failing heart.

Citation:
R.-P. Xiao, ß-Adrenergic Signaling in the Heart: Dual Coupling of the ß2-Adrenergic Receptor to Gs and Gi Proteins. Science's STKE (2001), http://stke.sciencemag.org/cgi/content/full/OC_sigtrans;2001/104/re15.

© 2001 American Association for the Advancement of Science

Citation: R.-P. Xiao, ß-Adrenergic Signaling in the Heart: Dual Coupling of the ß2-Adrenergic Receptor to Gs and Gi Proteins. Sci. STKE 2001, re15 (2001).

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