{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:52:50Z","timestamp":1760147570411,"version":"3.37.3"},"reference-count":53,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science (JSPS)","doi-asserted-by":"publisher","award":["25282024","25282024"],"award-info":[{"award-number":["25282024","25282024"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Food Science Institute Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2018,11,1]]},"abstract":"<jats:p> Intestinal cell line studies indicated luminal Na<jats:sup>+<\/jats:sup> homeostasis is essential for proton-coupled peptide absorption, because the driving force of PepT1 activity is supported by the apical Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup> exchanger NHE3. However, there is no direct evidence demonstrating the importance of in vivo luminal Na<jats:sup>+<\/jats:sup> for peptide absorption in animal experiments. To investigate the relationship between luminal Na<jats:sup>+<\/jats:sup> homeostasis and peptide absorption, we took advantage of claudin 15-deficient (cldn15<jats:sup>\u2212\/\u2212<\/jats:sup>) mice, whereby Na<jats:sup>+<\/jats:sup> homeostasis is disrupted. We quantitatively assessed the intestinal segment responsible for peptide absorption using radiolabeled nonhydrolyzable dipeptide (glycylsarcosine, Gly-Sar) and nonabsorbable fluid phase marker polyethylene glycol (PEG) 4000 in vivo. In wild-type (WT) mice, the concentration ratio of Gly-Sar to PEG 4000 decreased in the upper jejunum, suggesting the upper jejunum is responsible for peptide absorption. Gly-Sar absorption was decreased in the jejunum of cldn15<jats:sup>\u2212\/\u2212<\/jats:sup> mice. To elucidate the mechanism underlining these impairments, a Gly-Sar-induced short-circuit ( I<jats:sub>sc<\/jats:sub>) current was measured. In WT mice, increments of Gly-Sar-induced I<jats:sub>sc<\/jats:sub> were inhibited by the luminal application of a NHE3-specific inhibitor S3226 in a dose-dependent fashion. In contrast to in vivo experiments, robust Gly-Sar-induced I<jats:sub>sc<\/jats:sub> increments were observed in the jejunal mucosa of cldn15<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Gly-Sar-induced I<jats:sub>sc<\/jats:sub> was inhibited by S3226 or a reduction of luminal Na<jats:sup>+<\/jats:sup> concentration, which mimics low luminal Na<jats:sup>+<\/jats:sup> concentrations in vivo . Our study demonstrates that luminal Na<jats:sup>+<\/jats:sup> homeostasis is important for peptide absorption in native epithelia and that there is a cooperative functional relationship between PepT1 and NHE3. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Our study is the first to demonstrate that luminal Na<jats:sup>+<\/jats:sup> homeostasis is important for proton-coupled peptide absorption in in vivo animal experiments. <\/jats:p>","DOI":"10.1152\/ajpgi.00099.2018","type":"journal-article","created":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T17:16:47Z","timestamp":1535044607000},"page":"G799-G809","source":"Crossref","is-referenced-by-count":7,"title":["Luminal Na<sup>+<\/sup> homeostasis has an important role in intestinal peptide absorption in vivo"],"prefix":"10.1152","volume":"315","author":[{"given":"Noriko","family":"Ishizuka","sequence":"first","affiliation":[{"name":"Laboratory of Physiology School of Food and Nutritional Sciences, University of Shizuoka, Suruga-ku, 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