New insights into the regulation of angiotensin receptors.
OBJECTIVE
Angiotensin (Ang) II exerts its important physiological functions through two distinct receptor subtypes, type 1 (AT1) and type 2 (AT2) receptors. Recently, evidence has accumulated showing new mechanisms of regulation of Ang II receptor subtype functions beyond the classical actions of receptors for Ang II. These emerging concepts of regulation of Ang II receptors and a new insight into future drug discovery are discussed in this review.


RESULTS
New paradigms concerning functional regulation of the Ang receptors such as dimerization of Ang II receptors or other receptors and several novel receptor interacting proteins that interact with the intracellular C-terminal domain of the Ang II receptor have been reviewed, especially in terms of the pathophysiological roles of Ang II receptor functions. Moreover, ligand-independent receptor activation systems such as mechanical stretch for the AT1 receptor and agonistic antibodies against the AT1 receptor have also been highlighted.


CONCLUSIONS
Recently, new evidence has accumulated showing the existence of several novel receptor interacting proteins and various Ang II receptor activation mechanisms such as dimerization and mechanical stretch-induced activation, which differ from classical Ang II receptor signaling. These findings may provide new potent therapeutic targets for the treatment of cardiovascular disease.
Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Tohon, Ehime, Japan.
Masaki
M
Mogi
Masaru
M
Iwai
Masatsugu
M
Horiuchi
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D019281:Dimerization; D020690:GTPase-Activating Proteins / Q000502:physiology; D006801:Humans; D010766:Phosphorylation; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D011945:Receptors, Angiotensin / Q000737:chemistry / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology
C446513:ARAP1 protein, human; D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; C474762:MTUS1 protein, human; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D025521:Tumor Suppressor Proteins