Mechanisms of Prostaglandin-Stimulated Recovery of Mucosal Barrier Function in the Ischemia-Injured Porcine Intestine: Role of Intestinal Ion Transport

Abstract

A series of experiments were conducted to determine physiologic mechanisms of mucosal repair in the ischemia-injured intestine. The first experiment (Chapter III) investigated the contributory role of individual Cl- channels in the recovery of barrier function in ischemia-injured porcine ileum. Ischemia-injured porcine ileal mucosa was mounted in Ussing chambers. Short circuit current (Isc) and transepithelial resistance (TER) were measured in response to PGE2 and pharmacologic inhibitors of epithelial Cl- channels. Overall, results from these studies demonstrate that ClC-2-mediated intestinal Cl- secretion restores TER in ischemia-injured intestine. Chapter IV entails a study aimed at more directly investigating the role of ClC-2 in mucosal repair by evaluating mucosal repair in ischemia-injured intestinal mucosa mounted on Ussing chambers treated with the selective ClC-2 agonist, lubiprostone. Results from this suggest that activation of ClC-2 with the selective agonist, lubiprostone, stimulated elevations in TER and reduction in mannitol flux in the Ischemia-injured intestine. In Chapter V, experiments focused on the role of individual NHE isoforms in the recovery of barrier function in ischemia-injured porcine ileum. Results from this study demonstrate that inhibition of NHE2 activity, possibly via EBP50, induces recovery of barrier function in ischemic-injured intestine