This Article Full Text Full Text (PDF) All Versions of this Article: 48/2/173    most recent 01.HYP.0000232641.84521.92v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smith, N. J. Articles by Luttrell, L. M. Search for Related Content PubMed PubMed Citation Articles by Smith, N. J. Articles by Luttrell, L. M. Related Collections Cell signalling/signal transduction Physiological and pathological control of gene expression Smooth muscle proliferation and differentiation

(Hypertension. 2006;48:173.)
© 2006 American Heart Association, Inc.

Brief Reviews

Signal Switching, Crosstalk, and Arrestin Scaffolds

Novel G Protein–Coupled Receptor Signaling in Cardiovascular Disease

From the Molecular Endocrinology Laboratory (N.J.S.), Baker Heart Research Institute, Melbourne, Victoria, Australia; Departments of Medicine and Biochemistry and Molecular Biology (L.M.L.), Medical University of South Carolina, Charleston; and the Ralph H. Johnson Veterans Affairs Medical Center (L.M.L.), Charleston, SC.

Correspondence to Louis M. Luttrell, Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas St, 816 CSB, PO Box 250624, Charleston, SC 29425. E-mail luttrell@musc.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Hormone agonists, including angiotensin II (Ang II), norepinephrine, urotensin II, endothelin-1, vasopressin, and serotonin, mediate a plethora of physiological and pathological cardiovascular events via their cognate 7 membrane-spanning G protein–coupled receptors (GPCRs). On ligand binding, GPCRs undergo conformational changes that enable the activation and dissociation of heterotrimeric guanine nucleotide binding proteins (G proteins) and trigger a range of intracellular second messenger signaling cascades. Because of the immediacy of second messenger generation, GPCRs are able to acutely regulate cardiovascular events such as heart rate, contractile force, and systemic vascular resistance. Compelling evidence for GPCR control in the vasculature comes from both transgenic studies and clinical findings. For example, ß-adrenergic receptor blockers and inhibitors of the synthesis and binding of Ang II are proven antihypertensive therapeutics for humans. Furthermore, mice lacking RGS2, a regulatory protein that enhances the speed of GPCR signal termination, display marked hypertension, increased basal vascular tone, and hypersensitivity to vasoconstrictive agonists,¹ a phenotype that demonstrates the contribution of immediate GPCR-dependent signals, as well as the effect of GPCR dysregulation on cardiovascular homeostasis.

The evidence that signals emanating from GPCRs also contribute to the chronic development of vascular disease is persuasive. Overexpression of the Gq subunit in cardiomyocytes directly stimulates cardiac hypertrophy and decompensated heart failure,² whereas transgenic mice expressing an inhibitory fragment of Gq exhibit reduced hypertrophy in response to pressure overload.³ GPCR agonists like Ang II, endothelin-1, and norepinephrine, act directly on cardiomyocytes to stimulate hypertrophy.⁴ Meanwhile, Ang II contributes to atherosclerosis via activation of . . . [Full Text of this Article]

This article has been cited by other articles:

				N. J. Smith, L. A. Stoddart, N. M. Devine, L. Jenkins, and G. Milligan The Action and Mode of Binding of Thiazolidinedione Ligands at Free Fatty Acid Receptor 1 J. Biol. Chem., June 26, 2009; 284(26): 17527 - 17539. [Abstract] [Full Text] [PDF]

				L. Zhang, H. Zhao, Y. Qiu, H. H. Loh, and P.-Y. Law Src Phosphorylation of {micro}-Receptor Is Responsible for the Receptor Switching from an Inhibitory to a Stimulatory Signal J. Biol. Chem., January 23, 2009; 284(4): 1990 - 2000. [Abstract] [Full Text] [PDF]

				J. Davis, M. V. Westfall, D. Townsend, M. Blankinship, T. J. Herron, G. Guerrero-Serna, W. Wang, E. Devaney, and J. M. Metzger Designing Heart Performance by Gene Transfer Physiol Rev, October 1, 2008; 88(4): 1567 - 1651. [Abstract] [Full Text] [PDF]

				R. Mamillapalli, J. VanHouten, W. Zawalich, and J. Wysolmerski Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells J. Biol. Chem., September 5, 2008; 283(36): 24435 - 24447. [Abstract] [Full Text] [PDF]

				H. Ohtsu, S. Higuchi, H. Shirai, K. Eguchi, H. Suzuki, A. Hinoki, E. Brailoiu, A. D. Eckhart, G. D. Frank, and S. Eguchi Central Role of Gq in the Hypertrophic Signal Transduction of Angiotensin II in Vascular Smooth Muscle Cells Endocrinology, July 1, 2008; 149(7): 3569 - 3575. [Abstract] [Full Text] [PDF]

				X. Jiang, J. L. Benovic, and P. B. Wedegaertner Plasma Membrane and Nuclear Localization of G Protein coupled Receptor Kinase 6A Mol. Biol. Cell, August 1, 2007; 18(8): 2960 - 2969. [Abstract] [Full Text] [PDF]