Importance of gastric motility in the pathogenesis of indomethacin-induced gastric lesions in rats.
Effects of indomethacin on gastric motility and secretion, and levels of endogenous prostaglandins (PGs) were investigated in rats, in attempts to elucidate the factors involved in the pathogenesis of indomethacin-induced macroscopic gastric lesions. Subcutaneous administration of indomethacin had no effect on the gastric mucosa at doses of 1 and 5 mg/kg, but induced visible lesions dose dependently at over 10 mg/kg within 4 hr. At 25 mg/kg, there were apparent nonhemorrhagic lesions within 1 hr, and these lesions became hemorrhagic with time. Acid secretion was not affected by this agent at either dose level, but pepsin or acid-induced HCO3- secretion was significantly increased or decreased, respectively, at a dose less than 5 mg/kg, which did not induce any lesion. Gastric motility, however, was dose dependently increased after administration of indomethacin, and its effect was significant at 10 mg/kg or greater. Time-course changes in the motility were in parallel with those of the lesion formation. PGE2 and 6-keto PGF1 alpha levels in the corpus mucosa were reduced around 80-90% for more than 4 hr from 30 min after administration of 5 mg/kg or more of indomethacin. When all the above changes caused by indomethacin were plotted for the various doses, a significant correlation (r = 0.958, P less than 0.01) was found between the lesion index and the changes in motility, but not in other factors, including PG levels. These results indicate that gastric motility may be an important factor in the pathogenetic mechanism of indomethacin-induced gastric lesions in rats. A deficiency of endogenous PGs may be a prerequisite for later extension of the lesions.
Takeuchi
K
K
Ueki
S
S
Okabe
S
S
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D015232:Dinoprostone; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005769:Gastrointestinal Motility; D007213:Indomethacin / Q000633:toxicity*; D008297:Male; D011458:Prostaglandins E / Q000378:metabolism; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000503:physiopathology
D011458:Prostaglandins E; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D007213:Indomethacin