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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2532.)
© 2007 American Heart Association, Inc.

Brief Reviews

Emerging Concepts of Regulation of Angiotensin II Receptors

New Players and Targets for Traditional Receptors

Masaki Mogi; Masaru Iwai; Masatsugu Horiuchi

From the Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Japan.

Correspondence to Masatsugu Horiuchi, MD, PhD, FAHA, Professor and Chairman, Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295, Japan. E-mail horiuchi{at}m.ehime-u.ac.jp

Angiotensin (Ang) II exerts its important physiological functions through 2 distinct receptor subtypes, type 1 (AT₁) and type 2 (AT₂) receptors. Recently, new evidence has accumulated showing the existence of several novel receptor interacting proteins and various angiotensin II receptor activation mechanisms beyond the classical actions of receptors for Ang II. These associated proteins could contribute not only to Ang II receptors’ functions, but also to influencing pathophysiological states. Receptor dimerization of Ang II receptors such as homodimer, heterodimer, and complex formation with other G protein-coupled receptors has also been focused on as a new mechanism of their activation or inactivation. Moreover, ligand-independent receptor activation systems such as mechanical stretch for the AT₁ receptor have also been revealed. These emerging concepts of regulation of Ang II receptors and a new insight into future drug discovery are discussed in this review.

Recently, new evidence has accumulated showing the existence of several novel receptor interacting proteins and various angiotensin II receptor activation mechanisms such as dimerization and mechanical stretch-induced activation beyond the classical actions. In this review, these emerging concepts and a new insight into future drug discovery are discussed.

Key Words: angiotensin II receptor • angiotensin II type-1 receptor blocker • G protein-coupled receptor • interacting protein • dimerization

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