title: International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli [corrected].
abstract: The renin angiotensin system (RAS) produced hormone peptides regulate many vital body functions. Dysfunctional signaling by receptors for RAS peptides leads to pathologic states. Nearly half of humanity today would likely benefit from modern drugs targeting these receptors. The receptors for RAS peptides consist of three G-protein-coupled receptors—the angiotensin II type 1 receptor (AT1 receptor), the angiotensin II type 2 receptor (AT2 receptor), the MAS receptor—and a type II trans-membrane zinc protein—the candidate angiotensin IV receptor (AngIV binding site). The prorenin receptor is a relatively new contender for consideration, but is not included here because the role of prorenin receptor as an independent endocrine mediator is presently unclear. The full spectrum of biologic characteristics of these receptors is still evolving, but there is evidence establishing unique roles of each receptor in cardiovascular, hemodynamic, neurologic, renal, and endothelial functions, as well as in cell proliferation, survival, matrix-cell interaction, and inflammation. Therapeutic agents targeted to these receptors are either in active use in clinical intervention of major common diseases or under evaluation for repurposing in many other disorders. Broad-spectrum influence these receptors produce in complex pathophysiological context in our body highlights their role as precise interpreters of distinctive angiotensinergic peptide cues. This review article summarizes findings published in the last 15 years on the structure, pharmacology, signaling, physiology, and disease states related to angiotensin receptors. We also discuss the challenges the pharmacologist presently faces in formally accepting newer members as established angiotensin receptors and emphasize necessary future developments.
authors: Department of Molecular Cardiology, Lerner Research Institute of Cleveland Clinic, Cleveland, Ohio (S.S.K., H.U., J.R.K., K.C.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania (S.E.); Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium (P.M.L.V.); and Department of General Physiology, School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia (W.G.T.) karniks@ccf.org.
authors: Sadashiva S
authors: SS
authors: Karnik
authors: Department of Molecular Cardiology, Lerner Research Institute of Cleveland Clinic, Cleveland, Ohio (S.S.K., H.U., J.R.K., K.C.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania (S.E.); Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium (P.M.L.V.); and Department of General Physiology, School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia (W.G.T.).
authors: Hamiyet
authors: H
authors: Unal
authors: Department of Molecular Cardiology, Lerner Research Institute of Cleveland Clinic, Cleveland, Ohio (S.S.K., H.U., J.R.K., K.C.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania (S.E.); Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium (P.M.L.V.); and Department of General Physiology, School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia (W.G.T.).
authors: Jacqueline R
authors: JR
authors: Kemp
authors: Department of Molecular Cardiology, Lerner Research Institute of Cleveland Clinic, Cleveland, Ohio (S.S.K., H.U., J.R.K., K.C.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania (S.E.); Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium (P.M.L.V.); and Department of General Physiology, School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia (W.G.T.).
authors: Kalyan C
authors: KC
authors: Tirupula
authors: Department of Molecular Cardiology, Lerner Research Institute of Cleveland Clinic, Cleveland, Ohio (S.S.K., H.U., J.R.K., K.C.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania (S.E.); Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium (P.M.L.V.); and Department of General Physiology, School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia (W.G.T.).
authors: Satoru
authors: S
authors: Eguchi
authors: Department of Molecular Cardiology, Lerner Research Institute of Cleveland Clinic, Cleveland, Ohio (S.S.K., H.U., J.R.K., K.C.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania (S.E.); Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium (P.M.L.V.); and Department of General Physiology, School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia (W.G.T.).
authors: Patrick M L
authors: PM
authors: Vanderheyden
authors: Department of Molecular Cardiology, Lerner Research Institute of Cleveland Clinic, Cleveland, Ohio (S.S.K., H.U., J.R.K., K.C.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania (S.E.); Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium (P.M.L.V.); and Department of General Physiology, School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia (W.G.T.).
authors: Walter G
authors: WG
authors: Thomas
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000503:physiopathology; D049109:Cell Proliferation; D004727:Endothelium / Q000503:physiopathology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007674:Kidney Diseases / Q000503:physiopathology; D051379:Mice; D009422:Nervous System Diseases / Q000503:physiopathology; D011110:Polymorphism, Genetic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: C090830:AT4 receptor; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins