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

Abstract

We have previously shown that PGI2 and PGE2 have a synergistic role in restoring electrical transepithelial resistance ( R) in ischemia-injured porcine ileum via the second messengers Ca2+ and cAMP. Because Ca2+ and cAMP stimulate 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 solution. Addition of PGs stimulated a twofold increase in R, which was preceded by elevations in short-circuit current (increase of 25 μA/cm2). The PG-induced effect on R was partially inhibited with bumetanide, an inhibitor of Cl− secretion. The remaining elevations in R were similar in magnitude to those induced in ischemic tissues by amiloride, an inhibitor of Na+ absorption. Treatment with 10−4 M 8-bromo-cGMP or 300 mosM mucosal urea resulted in elevations in R similar to those attained with PG treatment. PGs signal recovery of Rvia induction of Cl−secretion and inhibition of Na+absorption, possibly by establishing a transmucosal osmotic gradient.

Prostaglandin-mediated inhibition of Na+/H+exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine

“…Histological evaluation of recovering ischemia-injured mucosa indicates that elevations in TER under the influence of NHE2 blockade were independent of the migratory phase of epithelial restitution. Therefore, improvements in TER were likely due to decreased permeability of the paracellular space, as has been demonstrated in previous studies (5,16,24). NHE2 and NHE3 were both expressed in enterocytes of the apical villus of the porcine ileum and were both upregulated immediately following ischemia, suggesting that expression patterns do not explain the differential effects on TER between the two isoforms.…”

“…Moreover, application of PG analogs (PGE 2 and PGI 2 ) to the ischemia-injured mucosa resulted in the rapid restoration of TER values to uninjured control levels (4 -6). Histological evaluation of recovering ischemia-injured tissues showed that the reparative events mediated by PGs in these studies appear to be related to permeability changes in the tight junctions and paracellular space rather than enhanced rates of epithelial restitution (5,16).…”

“…Our previous studies have demonstrated that PG-mediated recovery of barrier function is mechanistically linked to modulation of the interepithelial tight junctions and paracellular space rather than enhanced rates of epithelial restitution in ischemia-injured villi (5,16,2). To confirm that inhibition of NHE2 by HOE-694 influenced TER via similar mechanisms, we performed histological and morphometric analyses on ischemia-injured tissues at selected time points during recovery.…”

Transport of Water and Electrolytes through Epithelium of Colon and Expression CFTCR of Canals in Rats after 28-day Intake of Omeprazole

“…Адже, секреція хлору і слизу є основним механізмом підт-римання гомеостазу энтероцитів і створення захис-ного бар'єру слизової оболонки кишечника [10]. При таких умовах відбувається активація захисних механізмів, які включають в себе підвищення екс-пресії CFTR каналів, збільшення секреції води і слизу для забезпечення виштовхування патогенної мікрофлори зі слизової оболонки кишки та вида-лення її з порожнини назовні.…”

Nutraceutical Properties of Milk Fat Globular Membrane

“…In support of the oxidative stress hypothesis, one of the main MFGM proteins, xanthine oxidoreductase (XOR) can catalyze the formation of reactive oxygen (ROS) and nitrogen species (RNS), and is thought to be part of the innate immune system (Vorbach, Capecchi, and Penninger 2006). Perhaps not surprisingly, XOR has been implicated as a pathological factor in gut damage induced by ischemia/reperfusion injury via the generation of ROS and RNS (Blikslager, Roberts, and Argenzio 1999). These findings compelled us to determine the metal composition of the MFGM we isolated.…”