{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T17:08:38Z","timestamp":1773421718083,"version":"3.50.1"},"reference-count":55,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2013,8,15]]},"abstract":"<jats:p>Intestinal calcium (Ca<jats:sup>2+<\/jats:sup>) absorption occurs via paracellular and transcellular pathways. Although the transcellular route has been extensively studied, mechanisms mediating paracellular absorption are largely unexplored. Unlike passive diffusion, secondarily active paracellular Ca<jats:sup>2+<\/jats:sup>uptake occurs against an electrochemical gradient with water flux providing the driving force. Water movement is dictated by concentration differences that are largely determined by Na<jats:sup>+<\/jats:sup>fluxes. Consequently, we hypothesized that Na<jats:sup>+<\/jats:sup>absorption mediates Ca<jats:sup>2+<\/jats:sup>flux. NHE3 is central to intestinal Na<jats:sup>+<\/jats:sup>absorption. NHE3 knockout mice (NHE3<jats:sup>\u2212\/\u2212<\/jats:sup>) display impaired intestinal Na<jats:sup>+<\/jats:sup>, water, and Ca<jats:sup>2+<\/jats:sup>absorption. However, the mechanism mediating this latter abnormality is not clear. To investigate this, we used Ussing chambers to measure net Ca<jats:sup>2+<\/jats:sup>absorption across different segments of wild-type mouse intestine. The cecum was the only segment with net Ca<jats:sup>2+<\/jats:sup>absorption. Quantitative RT-PCR measurements revealed cecal expression of all genes implicated in intestinal Ca<jats:sup>2+<\/jats:sup>absorption, including NHE3. We therefore employed this segment for further studies. Inhibition of NHE3 with 100 \u03bcM 5-( N-ethyl- N-isopropyl) amiloride decreased luminal-to-serosal and increased serosal-to-luminal Ca<jats:sup>2+<\/jats:sup>flux. NHE3<jats:sup>\u2212\/\u2212<\/jats:sup>mice had a &gt;60% decrease in luminal-to-serosal Ca<jats:sup>2+<\/jats:sup>flux. Ussing chambers experiments under altered voltage clamps (\u221225, 0, +25 mV) showed decreased transcellular and secondarily active paracellular Ca<jats:sup>2+<\/jats:sup>absorption in NHE3<jats:sup>\u2212\/\u2212<\/jats:sup>mice relative to wild-type animals. Consistent with this, cecal Trpv6 expression was diminished in NHE3<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Together these results implicate NHE3 in intestinal Ca<jats:sup>2+<\/jats:sup>absorption and support the theory that this is, at least partially, due to the role of NHE3 in Na<jats:sup>+<\/jats:sup>and water absorption.<\/jats:p>","DOI":"10.1152\/ajpgi.00490.2012","type":"journal-article","created":{"date-parts":[[2013,6,14]],"date-time":"2013-06-14T05:53:34Z","timestamp":1371189214000},"page":"G303-G313","source":"Crossref","is-referenced-by-count":40,"title":["The Na<sup>+<\/sup>\/H<sup>+<\/sup>exchanger isoform 3 is required for active paracellular and transcellular Ca<sup>2+<\/sup>transport across murine cecum"],"prefix":"10.1152","volume":"305","author":[{"given":"Juraj","family":"Rievaj","sequence":"first","affiliation":[{"name":"Department of Physiology and Membrane Protein Disease Research Group, University of Alberta, Edmonton, Canada; 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