Modulating G protein-coupled receptors to effect reverse cardiac remodeling
© 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.
- Cardiac Remodeling: Molecular Mechanisms
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International Standard Book Number 13 (ISBN-13)
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