Indomethacin decreases resistance of gastric barrier to disruption by alcohol.
Using a canine chambered stomach preparation, the effects of three 30-min exposures of the gastric mucosa to 20% ethanol in 100 mN HCl on gastric mucosal barrier disruption and ulcer formation were assessed. The interval between exposures was 30 min. Following an initial exposure to 20% ethanol, the net fluxes of H+, Na+, and K+ ions and perfusate volume induced by a second and third exposure of the gastric epithelium to this damaging agent were significantly reduced. Only minimal ulceration was observed following the first exposure which did not worsen with subsequent exposure to ethanol. If indomethacin was given intravenously either before or immediately after the first ethanol exposure, recovery of barrier function was significantly lessened after this challenge, and the resistance to barrier disruption was significantly decreased during the two subsequent exposures to ethanol when compared to experiments in which mucosa was exposed to 20% ethanol without concomitant administration of indomethacin. In addition, marked mucosal ulceration was observed during the second and third ethanol exposures if indomethacin was given. These studies suggest that the first alcohol challenge may have elicited the synthesis and release of tissue prostaglandins and thereby enhanced resistance of the gastric mucosa to subsequent challenge by this damaging agent. When prostaglandin synthesis was blocked by indomethacin, the increased resistance to gastric injury did not occur.
D000287:Administration, Topical; D000818:Animals; D004285:Dogs; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D008297:Male; D011188:Potassium / Q000378:metabolism; D011448:Prostaglandin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013276:Stomach Ulcer / Q000139:chemically induced; D013997:Time Factors
D011448:Prostaglandin Antagonists; D000431:Ethanol; D012964:Sodium; D011188:Potassium; D007213:Indomethacin