Modulating G protein-coupled receptors to effect reverse cardiac remodeling

Published

Book Section

© Springer Science+Business Media New York 2013. All rights reserved. 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 ß-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.

Full Text

Duke Authors

Cited Authors

  • Perrino, C; Rockman, HA

Published Date

  • January 1, 2013

Book Title

  • Cardiac Remodeling: Molecular Mechanisms

Start / End Page

  • 159 - 177

International Standard Book Number 13 (ISBN-13)

  • 9781461459293

Digital Object Identifier (DOI)

  • 10.1007/978-1-4614-5930-9_10

Citation Source

  • Scopus