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Alzheimer's, angiotensin IV and an aminopeptidase

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Version 2 2024-06-13, 08:19
Version 1 2014-10-28, 09:29
journal contribution
posted on 2024-06-13, 08:19 authored by A Albiston, R Fernando, S Ye, G Peck, S Chai
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 or LVV-hemorphin 7 (LVV-H7) markedly enhances learning and memory in normal rodents and reverse memory deficits observed in animal models of amnesia. The high affinity binding site has a broad distribution in the brain including areas such as the hippocmapus that are involved in memory processing. The high affinity Ang IV binding site (AT4 receptor) has been identified as the transmembrane enzyme, insulin-regulated membrane aminopeptidase (IRAP). Insulin-regulated aminopeptidase is a type II integral membrane spanning protein belonging to the M1 family of aminopeptidases and in insulin-responsive cells colocalizes with GLUT4 in specific intra-cellular vesicles. Both Ang IV and LVV-H7 are competitive inhibitors of IRAP catalytic activity and are not substrates of the enzyme.

History

Journal

Biological and pharmaceutical bulletin

Volume

27

Pagination

765-767

Location

Tokyo, Japan

Open access

  • Yes

ISSN

0918-6158

eISSN

1347-5215

Language

eng

Publication classification

C2.1 Other contribution to refereed journal

Copyright notice

2004, Pharmaceutical Society of Japan

Issue

6

Publisher

Pharmaceutical Society of Japan