Emerging concepts of regulation of angiotensin II receptors: new players and targets for traditional receptors.
Angiotensin (Ang) II exerts its important physiological functions through 2 distinct receptor subtypes, type 1 (AT(1)) and type 2 (AT(2)) 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 AT(1) 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.
Mogi
Masaki
M
FAHA, Professor and Chairman, Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295, Japan.
Iwai
Masaru
M
Horiuchi
Masatsugu
M
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001323:Autoantibodies / Q000378:metabolism; D019281:Dimerization; D054314:Drug Inverse Agonism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008024:Ligands; D026901:Membrane Transport Proteins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D011487:Protein Conformation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001323:Autoantibodies; D051741:Kruppel-Like Transcription Factors; D008024:Ligands; D026901:Membrane Transport Proteins; D046912:Multiprotein Complexes; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D025521:Tumor Suppressor Proteins; D000804:Angiotensin II; D044763:Ubiquitin-Conjugating Enzymes; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D019204:GTP-Binding Proteins