The angiotensin IV/AT4 receptor

S. Y. Chai, R. Fernando, G. Peck, S. Y. Ye, F. A.O. Mendelsohn, T. A. Jenkins, A. L. Albiston

Research output: Contribution to journalReview ArticleResearchpeer-review

175 Citations (Scopus)

Abstract

The angiotensin AT4 receptor was originally defined as the specific, high-affinity binding site for the hexapeptide angiotensin IV (Ang IV). Subsequently, the peptide LVV-hemorphin 7 was also demonstrated to be a bioactive ligand of the AT4 receptor. Central administration of Ang IV its analogues or LVV-hemorphin 7 markedly enhance learning and memory in normal rodents and reverse memory deficits observed in animal models of amnesia. The AT4 receptor has a broad distribution and is found in a range of tissues, including the adrenal gland, kidney, lung and heart. In the kidney Ang IV increases renal cortical blood flow and decreases Na+ transport in isolated renal proximal tubules. The AT4 receptor has recently been identified as the transmembrane enzyme, insulin-regulated membrane aminopeptidase (IRAP). IRAP is a type II integral membrane spanning protein belonging to the M1 family of aminopeptidases and is predominantly found in GLUT4 vesicles in insulin-responsive cells. Three hypotheses for the memory-potentiating effects of the AT4 receptor/IRAP ligands, Ang IV and LVV-hemorphin 7, are proposed: (i) acting as potent inhibitors of IRAP, they may prolong the action of endogenous promnestic peptides; (ii) they may modulate glucose uptake by modulating trafficking of GLUT4; (iii) IRAP may act as a receptor, transducing the signal initiated by ligand binding to its C-terminal domain to the intracellular domain that interacts with several cytoplasmic proteins.

Original languageEnglish
Pages (from-to)2728-2737
Number of pages10
JournalCellular and Molecular Life Sciences
Volume61
Issue number21
DOIs
Publication statusPublished - 1 Nov 2004
Externally publishedYes

Keywords

  • GLUT4
  • Insulin-regulated aminopeptidase
  • Memory
  • Oxytocinase

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