@article{moeser_haskell_shifflett_little_schultz_blikslager_2004, title={CIC-2 chloride secretion mediates prostaglandin-induced recovery of barrier function in ischemia-injured porcine ileum}, volume={127}, ISSN={["1528-0012"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-4444353665&partnerID=MN8TOARS}, DOI={10.1053/j.gastro.2004.06.004}, abstractNote={BACKGROUND & AIMS
Ischemia results in the breakdown of the intestinal barrier, predisposing patients to sepsis and multiple organ failure. Prostaglandins play a critical role in mediating recovery of barrier function in ischemia-injured intestine through a mechanism involving stimulation of Cl - secretion. In the present study, we investigated the contributory role of individual Cl - channels in the recovery of barrier function in ischemia-injured porcine ileum.


METHODS
Ischemia-injured porcine ileal mucosa was mounted in Ussing chambers. Short-circuit current (Isc) and transepithelial resistance (TER) were measured in response to prostaglandin E 2 (PGE 2 ) and pharmacologic inhibitors of epithelial Cl - channels. Immunoassays were used to assess the expression and localization of ion channels.


RESULTS
Application of PGE 2 to ischemia-injured ileal mucosa stimulated increases in Isc, an indicator of Cl - secretion, that was followed by marked increases in TER, an indicator of barrier function recovery. In vitro studies revealed that although PGE 2 induced Cl - secretion via at least 3 distinct secretory pathways, recovery of barrier function was initiated by Cl - secretion via ClC-2 Cl - channels co-expressed with occludin and localized to tight junctions within restituting epithelium. Intravenous administration of furosemide to pigs subjected to 1 hour of ileal ischemia impaired recovery of barrier function, as evidenced by decreased TER and increased mucosal-to-serosal 3 H-mannitol flux after a 2-hour reperfusion/recovery period, confirming an important role for Cl - secretory pathways in vivo.


CONCLUSIONS
ClC-2-mediated intestinal Cl - secretion restores TER in ischemia-injured intestine. These data may provide the basis for targeted pharmacologic therapy for diseases associated with impaired barrier function.}, number={3}, journal={GASTROENTEROLOGY}, author={Moeser, AJ and Haskell, MM and Shifflett, DE and Little, D and Schultz, BD and Blikslager, AT}, year={2004}, month={Sep}, pages={802–815} }