title: Decrease in alkaline secretion during duodenal ulceration induced by mepirizole in rats.
abstract: The mechanisms by which the potent antiinflammatory agent, mepirizole, causes duodenal ulceration were investigated in the rat. After subcutaneous administration of 200 mg/kg of mepirizole, basal gastric acid secretion remained unchanged for 5 h but duodenal alkaline output, reliably measured, decreased significantly (p less than 0.05) within 2 h. The decrease was maximal (-45%) at 3 h and persisted for a total of 6 h. The duodenal alkaline secretion returned to near normal by 24 h. A dose-response study showed that the threshold ulcerogenic dose of mepirizole (30 mg/kg) did not significantly reduce alkaline secretion, whereas higher doses did. Plasma levels of immunoreactivity of gastrin, pancreatic polypeptide, vasoactive intestinal polypeptide, and secretin were not changed at either 6 or 24 h after oral mepirizole. Vasoactive intestinal peptide levels in the duodenal mucosa were increased by 158% at 24 h after administration. Secretin levels in the duodenal mucosa were decreased by greater than 60% at both 6 and 24 h after drug treatment. Intravenous secretin (1 CU/kg X h) had no effect on duodenal alkaline secretion in either saline- (154 mM NaCl) or mepirizole-treated animals. Exogenous 16,16-dimethyl prostaglandin E2 (10 micrograms/kg X h, i.v.) reversed the action of mepirizole on duodenal alkaline secretion. These findings suggest that mepirizole causes a reduction in duodenal alkaline secretion that can be reversed by administration of an exogenous prostaglandin.
mesh_terms: D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000468:Alkalies / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism*; D004840:Epirizole / Q000008:administration & dosage / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D005755:Gastrins / Q000097:blood; D007279:Injections, Subcutaneous; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012633:Secretin / Q000097:blood; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000097:blood
chemical_list: D000468:Alkalies; D005755:Gastrins; D011720:Pyrazoles; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D004840:Epirizole; D015064:16,16-Dimethylprostaglandin E2