Prostaglandin-induced recovery of barrier function in porcine ileum is triggered by chloride secretion.
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 microA/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 R via induction of Cl- secretion and inhibition of Na+ absorption, possibly by establishing a transmucosal osmotic gradient.
Blikslager
A T
AT
Department of Food Animal and Equine Medicine, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.
Roberts
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MC
Argenzio
R A
RA
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004553:Electric Conductivity; D017097:Electric Impedance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D007082:Ileum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013552:Swine
D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D002034:Bumetanide; C016276:8-bromocyclic GMP; D010042:Ouabain; C026678:carboprostacyclin; D000584:Amiloride; D011464:Epoprostenol; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin