Document Type
Article
Publication Date
4-15-2014
Publication Title
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology
Keywords
Erk1/2, PEP7, angiotensin II, angiotensin receptor, sodium intake
ISSN
0363-6119
Volume
306
Issue/No.
8
First Page
R619
Last Page
26
Abstract
A seven-amino acid peptide (PEP7) is encoded within a short open reading frame within exon 2 (E2) in the 5'-leader sequence (5'LS) upstream of the rat ANG 1a-receptor (rAT1aR) mRNA. A chemically synthesized PEP7 markedly inhibited ANG II-induced Erk1/2 activation in cell culture by 62% compared with a scrambled PEP7 (sPEP7) [pErk1/2/Erk1/2 (AU): ANG II, 1.000 ± 0.0, ANG II+PEP7, 0.3812 ± 0.086, ANG II+sPEP7, 1.069 ± 0.18; n = 3]. Under these same conditions, PEP7 had no effect on ANG II-stimulated inositol-trisphosphate production. PEP7 also had no effect on epidermal growth factor- and phorbol methyl ester-induced Erk1/2 activation, suggesting PEP7 selectively inhibits AT1aR-mediated Erk1/2 signaling. PEP7 intracerebroventricularly inhibited ANG II-induced saline intake but had no effect on water intake in male and female rats, indicating PEP7 also selectively inhibits the ANG II-Erk1/2 pathway in vivo since saline drinking is Erk1/2-mediated, while water drinking is not. PEP7 inhibition of ANG II-induced saline ingestion was rapidly reversed by a subsequent intracerebroventricular injection of an oxytocin antagonist, suggesting when PEP7 blocks ANG II-stimulated Erk1/2 activation, animals no longer ingest saline to balance the continued water intake, due to the release of oxytocin and its subsequent inhibitory effects on saline drinking. PEP7 also attenuated ANG II-induced increases in arterial pressure by 35% compared with sPEP7 at the same dose. Thus, we have identified a novel peptide encoded within the rAT1aR E2 that selectively inhibits Erk1/2 activation, resulting in physiological consequences for sodium ingestion and arterial pressure that may have implications for treating sodium-sensitive diseases like hypertension and chronic kidney disease.
NSUWorks Citation
Liu, Jun; Yosten, Gina L.; Ji, Hong; Zhang, Dan; Zheng, Wei; Speth, Robert C.; Samson, Willis K.; and Sandberg, Kathryn, "Selective inhibition of angiotensin receptor signaling through Erk1/2 pathway by a novel peptide" (2014). HPD Articles. 57.
https://nsuworks.nova.edu/hpd_facarticles/57
ORCID ID
0000-0002-6434-2158
DOI
10.1152/ajpregu.00562.2013
Copyright
Copyright © 2014 the American Physiological Society
