Regulation of angiotensin II receptors beyond the classical pathway.
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.
Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Tohon, Japan. email@example.com
SourceClinical science (London, England : 1979) 123:4 2012 Aug 1 pg 193-203
MeSHAdaptor Proteins, Signal Transducing
Angiotensin Receptor Antagonists
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Tumor Suppressor Proteins
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't