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(Circulation. 1999;100:579-582.)
© 1999 American Heart Association, Inc.

Editorials

New Insight Into the Role of Enhanced Adrenergic Receptor-Effector Coupling in the Heart

Arthur M. Feldman, MD, PhD; Charles McTiernan, PhD

From the Cardiovascular Institute of the UPMC Health System, Pittsburgh, Pa.

Correspondence to Arthur M. Feldman, MD, PhD, Harry S. Tack Professor of Medicine, Director, Cardiovascular Institute of the UPMC Health System, 200 Lothrop St, S-572 Scaife Hall, Pittsburgh, PA 15213. E-mail feldmanam@msx.upmc.edu

Key Words: Editorials • receptors, adrenergic, beta • stress • heart failure • proteins

	Introduction

 
The ability of the heart to augment the perfusion of vital organs and skeletal muscles during stress is predicated on its ability to increase contractility in response to adrenergic neurohormones that are released from postsynaptic nerve terminals within the heart and/or from the adrenal gland. These neurohormonal signals must then be detected and processed by a complex of proteins located within the sarcolemmal membrane, resulting in the conversion of the adrenergic signal to an alteration in the biomechanical properties of individual myocytes. This sarcolemmal protein complex consists of adrenergic receptors (ARs), guanine nucleotide–binding regulatory proteins, and the effector enzyme adenylyl cyclase. Myocardial contractility is augmented by the interaction of adrenergic agonists with ß₁- and/or ß₂-adrenergic receptors (ßARs) located on the surface of the sarcolemmal membrane (see review in Reference 1¹ ). These 2 ßAR subtypes are coupled to adenylyl cyclase activation by the stimulatory guanine nucleotide–binding protein (G_s). Interaction of the agonist-ßAR complex with the heterotrimeric G protein catalyzes the release of GDP from the -subunit of the G protein (_s), allowing the binding of GTP and the subsequent activation of adenylyl cyclase by _s-GTP. This activation persists until intrinsic GTPase activity of _s hydrolyzes the nucleotide, resulting in an inactive _s-GDP moiety.¹ G-protein–mediated activation of adenylyl cyclase effects the synthesis of the intracellular second messenger cAMP and the resulting phosphorylation of a cAMP-dependent protein kinase (PKA). Once phosphorylated, PKA is then able to effect positive inotropic and chronotropic responses by phosphorylating a group of intracellular proteins, . . . [Full Text of this Article]

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