title: Regulation of angiotensin II receptors beyond the classical pathway.
abstract: The RAS (renin-angiotensin system) plays a role not only in the cardiovascular system, including blood pressure regulation, but also in the central nervous system. AngII (angiotensin II) binds two major receptors: the AT(1) receptor (AngII type 1 receptor) and AT(2) receptor (AngII type 2 receptor). It has been recognized that AT(2) receptor activation not only opposes AT(1) receptor actions, but also has unique effects beyond inhibitory cross-talk with AT(1) receptor signalling. Novel pathways beyond the classical actions of RAS, the ACE (angiotensin-converting enzyme)/AngII/AT(1) receptor axis, have been highlighted: the ACE2/Ang-(1-7) [angiotensin-(1-7)]/Mas receptor axis as a new opposing axis against the ACE/AngII/AT(1) receptor axis, novel AngII-receptor-interacting proteins and various AngII-receptor-activation mechanisms including dimer formation. ATRAP (AT(1)-receptor-associated protein) and ATIP (AT(2)-receptor-interacting protein) are well-characterized AngII-receptor-associated proteins. These proteins could regulate the functions of AngII receptors and thereby influence various pathophysiological states. Moreover, the possible cross-talk between PPAR (peroxisome-proliferator-activated receptor)-γ and AngII receptor subtypes is an intriguing issue to be addressed in order to understand the roles of RAS in the metabolic syndrome, and interestingly some ARBs (AT(1)-receptor blockers) have been reported to have an AT(1)-receptor-blocking action with a partial PPAR-γ agonistic effect. These emerging concepts concerning the regulation of AngII receptors are discussed in the present review.
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Tohon, Japan. horiuchi@m.ehime-u.ac.jp
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Jun
authors.initials: J
authors.lastname: Iwanami
authors.forename: Masaki
authors.initials: M
authors.lastname: Mogi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000502:physiology; D006801:Humans; D047495:PPAR gamma / Q000819:agonists / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: C449676:AGTRAP protein, human; C446513:ARAP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D057911:Angiotensin Receptor Antagonists; D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; C474762:MTUS1 protein, human; D047495:PPAR gamma; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D025521:Tumor Suppressor Proteins; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D007703:Peptidyl-Dipeptidase A