New insights into the regulation of angiotensin receptors

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.