Functional selectivity in adrenergic and angiotensin signaling systems.


Journal Article (Review)

β-Adrenergic and angiotensin II type 1A receptors are therapeutic targets for the treatment of a number of common human diseases. Pharmacological agents designed as antagonists for these receptors have positively affected the morbidity and mortality of patients with hypertension, heart failure, and renal disease. Antagonism of these receptors, however, may only partially explain the therapeutic benefits of β-blockers and angiotensin receptor blockers given the emerging concept of functional selectivity or biased agonism. This new pharmacological paradigm suggests that multiple signaling pathways can be differentially modified by a single ligand-receptor interaction. This review examines the functional selectivity of β-adrenergic and angiotensin II type 1A receptors with respect to their ability to signal via both G protein-dependent and G protein-independent mechanisms, with a focus on the multifunctional protein β-arrestin. Also highlighted are the concept of "biased signaling" through β-arrestin mediated pathways, the affect of ligand/receptor modification on such biased agonism, and the implications of functional selectivity for the development of the next generation of β-blockers and angiotensin receptor blockers.

Full Text

Duke Authors

Cited Authors

  • Patel, CB; Noor, N; Rockman, HA

Published Date

  • December 2010

Published In

Volume / Issue

  • 78 / 6

Start / End Page

  • 983 - 992

PubMed ID

  • 20855464

Pubmed Central ID

  • 20855464

Electronic International Standard Serial Number (EISSN)

  • 1521-0111

Digital Object Identifier (DOI)

  • 10.1124/mol.110.067066


  • eng

Conference Location

  • United States