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We aimed to investigate whether transient receptor potential vanilloid 4 (TRPV4) channels and Na\n                    <jats:sup>+<\/jats:sup>\n                    \/Ca\n                    <jats:sup>2+<\/jats:sup>\n                    exchanger 1 (NCX1) are critical for enterohormone secretion and whether they are involved in IBS. Ca\n                    <jats:sup>2+<\/jats:sup>\n                    imaging and patch\u2010clamp were applied to STC\u20101. IBS\u2010diarrhea (IBS\u2010D) mouse model was established by wrap restraint stress (WRS). Western blot verified TRPV4 and NCX1 expressions in STC\u20101; co\u2010immunoprecipitation demonstrated their physical interaction, and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    imaging and patch\u2010clamp confirmed function and interaction. Carbachol (CCh), a stable analog of acetylcholine (ACh), induced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling and currents in EECs via a functional coupling of TRPV4 and NCX1. Moreover, intestinal cholecystokinin (CCK) transcripts in IBS\u2010D mice were significantly increased, and ACh enhanced intestinal CCK secretion in mice, all of which could be abolished by blockers of TRPV4, NCX1, and CCK receptors. Finally, these blockers alleviated the severity of IBS\u2010D in mice. We reveal a novel TRPV4\/NCX1\/Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \/CCK pathway in EECs, which is involved in the pathogenesis of IBS\u2010D. Targeting this pathway may hold promise for the prevention\/treatment of IBS\u2010D.\n                  <\/jats:p>","DOI":"10.14814\/phy2.71149","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T07:21:40Z","timestamp":1792480900000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TRPV4<\/scp>\n                    \/\n                    <scp>NCX1<\/scp>\n                    coupling regulates Ca\n                    <sup>2+<\/sup>\n                    \u2010dependent cholecystokinin secretion from enteroendocrine cells to involve the pathogenesis of irritable bowel syndrome\u2010diarrhea in male mice"],"prefix":"10.14814","volume":"14","author":[{"given":"Jianxin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Qingdao University Medical College  Qingdao 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