{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:39:17Z","timestamp":1792715957203,"version":"4.5.0"},"reference-count":40,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2014,4,15]]},"abstract":"<jats:p>A seven-amino acid peptide (PEP7) is encoded within a short open reading frame within exon 2 (E2) in the 5\u2032-leader sequence (5\u2032LS) upstream of the rat ANG 1a-receptor (rAT<jats:sub>1a<\/jats:sub>R) 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 \u00b1 0.0, ANG II+PEP7, 0.3812 \u00b1 0.086, ANG II+sPEP7, 1.069 \u00b1 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 AT<jats:sub>1a<\/jats:sub>R-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 rAT<jats:sub>1a<\/jats:sub>R 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.<\/jats:p>","DOI":"10.1152\/ajpregu.00562.2013","type":"journal-article","created":{"date-parts":[[2014,2,13]],"date-time":"2014-02-13T02:36:23Z","timestamp":1392258983000},"page":"R619-R626","source":"Crossref","is-referenced-by-count":18,"title":["Selective inhibition of angiotensin receptor signaling through Erk1\/2 pathway by a novel peptide"],"prefix":"10.1152","volume":"306","author":[{"given":"Jun","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Georgetown University, Washington, D.C.;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina L. 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