Unbound MEDLINE

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.

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  • Publisher Full Text

    • Authors

    Horiuchi M, Iwanami J, Mogi M

    Institution

    Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Tohon, Japan. horiuchi@m.ehime-u.ac.jp

    Source

    Clinical science (London, England : 1979) 123:4 2012 Aug 1 pg 193-203

    MeSH

    Adaptor Proteins, Signal Transducing
    Angiotensin Receptor Antagonists
    Animals
    Carrier Proteins
    GTPase-Activating Proteins
    Humans
    PPAR gamma
    Peptidyl-Dipeptidase A
    Protein Tyrosine Phosphatase, Non-Receptor Type 6
    Receptor, Angiotensin, Type 1
    Receptor, Angiotensin, Type 2
    Receptors, Angiotensin
    Renin-Angiotensin System
    Signal Transduction
    Tumor Suppressor Proteins

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    22548405