Biased agonism of the angiotensin II type 1 receptor.
G protein-coupled receptors (GPCRs) can be activated by multiple ligands and exhibit the capacity to couple to numerous intracellular signal transduction pathways. This property allows GPCRs to be modulated by biased agonists that selectively activate specific subsets of GPCR-regulated cellular signaling proteins. The angiotensin II type 1 receptor (AT1R) is a GPCR that endogenously binds to the peptide ligand angiotensin II. More recently it has been demonstrated that a modified peptide, [Sar1I-le4-Ile8]-angiotensin II (SII) acts as a biased agonist towards the AT1R. SII binds to the AT1R without promoting heterotrimeric G protein-coupling, but serves to link the receptor to the beta-arrestin-dependent activation of the mitogen activated protein kinase pathway. The present mini-review summarizes current knowledge regarding the role of biased agonists in stimulating biased AT1R signaling.
J. Allyn Taylor Centre for Cell Biology, Molecular Brain Research Group, Robarts Research Institute and the Department of Physiology & Pharmacology, The University of Western Ontario 100 Perth Dr. London, Ontario, N6A 5K8, Canada.
C M
CM
Godin
S S G
SS
Ferguson
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000378:metabolism / Q000494:pharmacology; D019390:Arrestins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D019808:Losartan / Q000378:metabolism / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D011487:Protein Conformation; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists* / Q000378:metabolism; D013314:Stress, Mechanical; D000071557:beta-Arrestins
D047228:Angiotensin II Type 1 Receptor Blockers; D019390:Arrestins; D008024:Ligands; D044140:Receptor, Angiotensin, Type 1; D000071557:beta-Arrestins; D000804:Angiotensin II; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D019808:Losartan