Role of prostanoids in experimental duodenal ulcer in rat.
The purposes of this study were to determine whether inhibition of cyclooxygenase is a mechanism by which cysteamine and mepirizole produce duodenal ulcers, identify qualitative or quantitative differences in prostanoid production between gastric mucosa and duodenum, and determine whether differences in cyclooxygenase sensitivity to inhibition by aspirin exist between these two tissues. In fed female rats, gastric mucosal prostaglandin E2 (PGE2) and prostacyclin (PGI2) generation was 235 +/- 25 and 832 +/- 40 ng/g/min, respectively, whereas full-thickness duodenal PGE2 and PGI2 generation was 665 +/- 46 and 662 +/- 49 ng/g/min, respectively. Over an intraperitoneal dose range of 0-25 mg/kg, aspirin-induced cyclooxygenase inhibition was dose-dependent and similar for the two tissues. Duodenal ulceration (16.7 mm2) produced by cysteamine, 425 mg/kg, was associated with a 46% reduction in duodenal PGE2 generation, while having no effect on PGI2 generation; however, cysteamine, 213 mg/kg, produced no visible duodenal mucosa injury yet reduced duodenal PGE2 generation 39% compared to control values. In fed male rats, gastric mucosal PGE2 and PGI2 generation was 179 +/- 18 and 813 +/- 61 ng/g/min, respectively, whereas duodenal PGE2 and PGI2 generation was 321 +/- 27 and 454 +/- 38 ng/g/min, respectively. Duodenal ulceration (7.7 +/- 2.3 mm2) produced by oral mepirizole was associated with a 63% reduction in duodenal PGE2 generation compared to control values, while having no effect on PGI2 generation. Subcutaneous aspirin, 100 mg/kg, which reduced duodenal PGE2 generation to a greater degree than either ulcerogen, given in conjunction with pentagastrin, did not produce visible duodenal ulceration.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001241:Aspirin / Q000633:toxicity; D016861:Cyclooxygenase Inhibitors; D003543:Cysteamine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000503:physiopathology*; D004386:Duodenum / Q000187:drug effects / Q000201:enzymology; D004840:Epirizole / Q000633:toxicity; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D004840:Epirizole; D003543:Cysteamine; D001241:Aspirin