Modulating G Protein-Coupled Receptors to Effect Reverse Cardiac Remodeling

Chapter
First Online:
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 5)

Abstract

G protein-coupled receptors (GPCRs) represent the largest known family of transmembrane receptors and therapeutic targets in cardiovascular medicine, accounting for a large number of marketed cardiovascular pharmaceuticals. Traditionally, GPCR stimulation promotes G protein signaling and, to limit unrestrained stimulation, activation of G protein-coupled receptor kinases (GRKs), leading to agonist-dependent receptor phosphorylation. In turn, GPCR phosphorylation promotes β-arrestin binding to the receptors, which sterically prevents further G protein signaling and scaffold receptors to the internalization machinery. However, novel aspects of GPCR signaling have been recently appreciated, including G protein modulators, G protein-independent pathways, and GRK adrenal modulation of adrenergic drive. Since all currently used drugs have been developed using assays only testing G protein-dependent effects, the discovery of such novel signal transduction pathways might represent an important opportunity to identify additional therapeutic approaches to reverse or prevent cardiac remodeling and failure.

Keywords

G proteins Receptors Cardiac remodeling Arrestins Hypertrophy Heart failure Signaling 
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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Clinical Medicine, Cardiovascular and Immunological SciencesFederico II UniversityNaplesItaly
  2. 2.Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Department of Medicine, Department of Cell Biology, Department of Molecular GeneticsDuke University Medical CenterDurhamUSA

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