Cellular and Molecular Life Sciences CMLS

, Volume 61, Issue 21, pp 2728–2737

What’s new in the renin-angiotensin system?

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
Multi-author Review

DOI: 10.1007/s00018-004-4246-1

Cite this article as:
Chai, S.Y., Fernando, R., Peck, G. et al. CMLS, Cell. Mol. Life Sci. (2004) 61: 2728. doi:10.1007/s00018-004-4246-1

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.

Key words.

Insulin-regulated aminopeptidase oxytocinase memory GLUT4 

Copyright information

© Birkhäuser Verlag, Basel 2004

Authors and Affiliations

  • S. Y. Chai
    • 1
    • 2
  • R. Fernando
    • 1
    • 3
  • G. Peck
    • 1
    • 4
  • S. -Y. Ye
    • 1
    • 5
  • F. A. O. Mendelsohn
    • 1
  • T. A. Jenkins
    • 1
  • A. L. Albiston
    • 1
  1. 1.Neurochemistry, Howard Florey InstituteThe University of MelbourneParkvilleAustralia
  2. 2.Department of Anatomy and Cell BiologyThe University of MelbourneParkvilleAustralia
  3. 3.Department of GeneticsThe University of MelbourneParkvilleAustralia
  4. 4.Department of Medicine, Royal Melbourne HospitalThe University of MelbourneParkvilleAustralia
  5. 5.Department of BiochemistryThe University of MelbourneParkvilleAustralia

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