Effect of prostaglandin inhibitors on bile salt-induced mucosal damage of porcine colon.
The effect of endogenous prostaglandin inhibition on bile salt-induced colonic injury and secretion was studied microscopically and by measurements of [14C]mannitol clearance and transmural potential difference in vivo. Bile salt-induced mucosal damage and permeability increased sequentially with concentration, and these degenerative changes were accelerated with the cyclooxygenase inhibitor indomethacin. Mepacrine, a phospholipase inhibitor, gave similar results, whereas nordihydroguaiaretic acid, a lipoxygenase inhibitor, was ineffective. The effect of indomethacin was abolished by prostaglandin E2 replacement; however, exogenous prostaglandin or prior bile salt exposure failed to result in additional protection. Concentrations of bile salts below the threshold for damage elicited net secretion in the presence or absence of indomethacin, and indomethacin was also without effect on the bile salt-induced secretion at damaging concentrations. Restitution of a completely denuded surface was unaffected by indomethacin, and occurred within 30 min of recovery. The present evidence suggests that endogenous prostaglandins render the mucosa more resistant to acute injury by events independent of the repair process. In addition, the bile salt-induced secretion, which can be dissociated from increased mucosal permeability and microscopic damage, is unlikely to be the result of increased mucosal synthesis of prostaglandins.
Argenzio
R A
RA
Department of Anatomy, College of Veterinary Medicine, North Carolina State University, Raleigh.
Henrikson
C K
CK
Liacos
J A
JA
D000818:Animals; D001834:Body Water / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003840:Deoxycholic Acid / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008353:Mannitol / Q000493:pharmacokinetics; D009637:Masoprocol / Q000494:pharmacology; D010539:Permeability; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011796:Quinacrine / Q000494:pharmacology; D013552:Swine
D011448:Prostaglandin Antagonists; D003840:Deoxycholic Acid; D008353:Mannitol; D009637:Masoprocol; D011796:Quinacrine; D015232:Dinoprostone; D007213:Indomethacin