Role of prostaglandin deficiency in pathogenetic mechanism of gastric lesions induced by indomethacin in rats.
The present study was undertaken in rats using 2-deoxy-D-glucose (2DG) as a stimulator of gastric motility and a low dose of indomethacin as a prostaglandin (PG) synthesis inhibitor to investigate the roles of gastric motility and PG deficiency in the pathogenesis of indomethacin-induced gastric lesions. Subcutaneously administered indomethacin at 5 mg/kg did not induce any visible damage in the mucosa within 4 hr, but at 25 mg/kg produced linear hemorrhagic lesions along the long axis of the stomach. 2DG (100 mg/kg/hr), given intravenously, produced linear nonhemorrhagic lesions along the mucosal folds and, in the presence of 5 mg/kg of indomethacin, caused severe hemorrhagic lesions in the same areas of the stomach. Gastric motility was markedly enhanced by both indomethacin (25 mg/kg) and 2DG, while acid output and mucosal blood flow were increased only by the latter. Mucosal PGE2 levels were significantly reduced by indomethacin (25 mg/kg) but not by 2DG. Indomethacin at 5 mg/kg alone had no or little effect on any parameter except PG levels, which were reduced to similar degrees as caused by 25 mg/kg of the agent. Time-course development of the lesions was closely associated with those changes in gastric motility after administration of indomethacin (25 mg/kg) and 2DG. These results suggest that the enhanced gastric motility is, by itself, sufficient to induce damage (nonhemorrhagic) in the mucosa and that a PG deficiency alone does not induce any damage but is required for further extension to hemorrhagic lesions of nonhemorrhagic ones that are initially induced by enhanced gastric motility.(ABSTRACT TRUNCATED AT 250 WORDS)
Okada
M
M
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Niida
H
H
Takeuchi
K
K
Okabe
S
S
D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000032:analysis / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D005769:Gastrointestinal Motility / Q000187:drug effects; D007213:Indomethacin / Q000633:toxicity*; D008297:Male; D011448:Prostaglandin Antagonists; D011453:Prostaglandins / Q000032:analysis / Q000172:deficiency*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors
D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D003847:Deoxyglucose; D007213:Indomethacin