Blikslager. Recovery of Mucosal Barrier Function in Ischemic Porcine Ileum and Colon

is Stimulated by a Novel Agonist of the ClC-2 Chloride Channel, Lubiprostone-Previous studies utilizing an ex vivo porcine model of intestinal ischemic injury demonstrated that PGE2 stimulates repair of mucosal barrier function via a mechanism involving chloride (Cl-) secretion and reductions in paracellular permeability. Further experiments revealed that the signaling mechanism for PGE2-induced mucosal recovery was mediated via type-2 chloride 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 ischemic-injured intestinal mucosa treated with the selective ClC-2 agonist, lubiprostone. Ischemic-injured porcine ileal mucosa was mounted in Ussing chambers and short circuit current (Isc) and transepithelial electrical resistance (TER) were measured in response to lubiprostone. Application of 0.01µM – 1µM lubiprostone to ischemic-injured mucosa induced concentration-dependent increases in TER, with 1µM lubiprostone stimulating a 2-fold increase in TER (TER = 26 ·cm2, p<0.01). However, lubiprostone (1µM) stimulated higher elevations in TER despite lower Isc responses compared with the non-selective secretory agonist, PGE2 (1µM). Furthermore