Journal
PEPTIDES
Volume 63, Issue -, Pages 30-37Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2014.10.016
Keywords
Angiotensin IV; Atrial natriuretic peptide; Heart; Insulin-regulated aminopeptidase; Signal pathwaya
Funding
- Ministry of Science and Technology (MoST)/Korea Science & Engineering Foundation (KOSEF) [2010-0021808]
- National Research Foundation of Korea [2010-0021808] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Angiotensin IV (Ang IV) is formed by aminopeptidase N (APN) from angiotensin III (Ang III) by removing the first N-terminal amino acid. Previouslt, we reported that angiotensin II (Ang II) inhibits atrial natriuretic peptide (ANP) secretion via angiotensin II type 1 receptor (AT(1)R). In contrast, angiotensin( 1-7) [Ang-(1-7)] and Ang III stimulate ANP secretion via Mas receptor (Mas R) and angiotensin II type 2 receptor (AT(2)R), respectively. However, it is not known whether there is any relationship between AngIV and ANP secretion. Therefore, the aim of the present study was to determine the effect of Ang IV on ANP secretion and to find its downstream signaling pathway using in isolated perfused beating atria. AngIV (0.1, 1 and 10 mu M) stimulated high atrial stretch-induced ANP secretion and ANP concentration in a dose-dependent manner. The augmented effect of Ang IV (1 mu M) on high atrial stretch-induced ANP secretion and concentration was attenuated by pretreatment with insulin-regulated aminopeptidase (IRAP) antagonist but not by AT(1)R or AT(2)R antagonist. Pretreatment with inhibitors of downstream signaling pathway including phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and mammalian target of rapamycin (mTOR) blocked Ang IV-induced ANP secretion and concentration. Therefore, these results suggest that Ang IV stimulates ANP secretion and concentration via IRAP and PI3K-Akt-mTOR pathway. (C) 2014 Elsevier Inc. All rights reserved.
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