Prostaglandin-induced recovery of barrier function in porcine ileum is triggered by chloride secretion

We have previously shown that PGI(2) and PGE(2) have a synergistic role in restoring electrical transepithelial resistance (R) in ischemia-injured por cine ileum via the second messengers Ca2+ and cAMP. Because Ca2+ and cAMP s timulate Cl- secretion, we assessed the role of PG-induced Cl- secretion in recovery of R. Mucosa from porcine ileum subjected to ischemia for 45 min was mounted in Ussing chambers and bathed in indomethacin and Ringer soluti on. Addition of PGs stimulated a twofold increase in R, which was preceded by elevations in short-circuit current (increase of 25 mu A/cm(2)). The PG- induced effect on R was partially inhibited with bumetanide, an inhibitor o f Cl- secretion. The remaining elevations in R were similar in magnitude to those induced in ischemic tissues by amiloride, an inhibitor of Na+ absorp tion. Treatment with 10(-4) M 8-bromo-cGMP or 300 mosM mucosal urea resulte d in elevations in R similar to those attained with PG treatment. PGs signa l recovery of R via induction of Cl- secretion and inhibition of Na+ absorp tion, possibly by establishing a transmucosal osmotic gradient.