title: Functional relevance of biased signaling at the angiotensin II type 1 receptor.
abstract: Angiotensin II type 1 receptor antagonists (AT1R blockers, or ARBs) are used commonly in the treatment of cardiovascular disorders such as heart failure and hypertension. Their clinical success arises from their ability to prevent deleterious Gα(q) protein activation downstream of AT1R, which leads to a decrease in morbidity and mortality. Recent studies have identified AT1R ligands that concurrently inhibit Gα(q) protein-dependent signaling and activate Gα(q) protein-independent/β-arrestin-dependent signaling downstream of AT1R, events that may actually improve cardiovascular performance more than conventional ARBs. The ability of such ligands to induce intracellular signaling events in an AT1R-β-arrestin-dependent manner while preventing AT1R-Gα(q) protein activity defines them as biased AT1R ligands. This mini-review will highlight recent studies that have defined biased signaling at the AT1R and discuss the possible clinical relevance of β-arrestin-biased AT1R ligands in the cardiovascular system.
authors.affiliation: Department of Pharmaceutical Sciences, Jefferson School of Pharmacy, Thomas Jefferson University, Philadelphia, PA 1917, USA. douglas.tilley@jefferson.edu
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Tilley
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D054333:Drug Partial Agonism; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists* / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: D008024:Ligands; D044140:Receptor, Angiotensin, Type 1; D004815:Epidermal Growth Factor