{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T16:56:10Z","timestamp":1773420970182,"version":"3.50.1"},"reference-count":59,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:p>Previous studies utilizing an ex vivo porcine model of intestinal ischemic injury demonstrated that prostaglandin (PG)E<jats:sub>2<\/jats:sub>stimulates repair of mucosal barrier function via a mechanism involving Cl<jats:sup>\u2212<\/jats:sup>secretion and reductions in paracellular permeability. Further experiments revealed that the signaling mechanism for PGE<jats:sub>2<\/jats:sub>-induced mucosal recovery was mediated via type-2 Cl<jats:sup>\u2212<\/jats:sup>channels (ClC-2). Therefore, the objective of the present study was to directly investigate the role of ClC-2 in mucosal repair by evaluating mucosal recovery in ischemia-injured intestinal mucosa treated with the selective ClC-2 agonist lubiprostone. Ischemia-injured porcine ileal mucosa was mounted in Ussing chambers, and short-circuit current ( I<jats:sub>sc<\/jats:sub>) and transepithelial electrical resistance (TER) were measured in response to lubiprostone. Application of 0.01\u20131 \u03bcM lubiprostone to ischemia-injured mucosa induced concentration-dependent increases in TER, with 1 \u03bcM lubiprostone stimulating a twofold increase in TER (\u0394TER = 26 \u03a9\u00b7cm<jats:sup>2<\/jats:sup>; P &lt; 0.01). However, lubiprostone (1 \u03bcM) stimulated higher elevations in TER despite lower I<jats:sub>sc<\/jats:sub>responses compared with the nonselective secretory agonist PGE<jats:sub>2<\/jats:sub>(1 \u03bcM). Furthermore, lubiprostone significantly ( P &lt; 0.05) reduced mucosal-to-serosal fluxes of<jats:sup>3<\/jats:sup>H-labeled mannitol to levels comparable to those of normal control tissues and restored occludin localization to tight junctions. Activation of ClC-2 with the selective agonist lubiprostone stimulated elevations in TER and reductions in mannitol flux in ischemia-injured intestine associated with structural changes in tight junctions. Prostones such as lubiprostone may provide a selective and novel pharmacological mechanism of accelerating recovery of acutely injured intestine compared with the nonselective action of prostaglandins such as PGE<jats:sub>2<\/jats:sub>.<\/jats:p>","DOI":"10.1152\/ajpgi.00183.2006","type":"journal-article","created":{"date-parts":[[2006,10,20]],"date-time":"2006-10-20T01:30:26Z","timestamp":1161307826000},"page":"G647-G656","source":"Crossref","is-referenced-by-count":89,"title":["Recovery of mucosal barrier function in ischemic porcine ileum and colon is stimulated by a novel agonist of the ClC-2 chloride channel, lubiprostone"],"prefix":"10.1152","volume":"292","author":[{"given":"Adam J.","family":"Moeser","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prashant K.","family":"Nighot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kory 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