Effects of prostaglandin D2 and omeprazole on indomethacin-induced gastric ulcers in rats.
1. The mechanism of indomethacin-induced gastric ulcers was investigated by measuring tissue prostaglandins (PG) levels. 2. The effects of PGD2 and omeprazole, an H+ pump inhibitor, were also estimated. 3. Four kinds of PG--6-keto PGF1 alpha, PGF2 alpha, and PGD2--in rat gastric mucosa were measured by high performance liquid chromatography. 4. All PG levels decreased 1 h after oral administration of 2 mg/kg indomethacin, although they recovered considerably 24 h after administration. No gastric ulcers were observed throughout the experiments in rats treated with 2 mg/kg indomethacin. 5. All PG were not detected 1 h, and even 24 h after administration of 12 mg/kg indomethacin. Over 6 h after administration, gastric ulcers were observed. 6. Premedication with omeprazole prevented ulcer formation, although it did not improve gastric mucosal PG levels. Administration of PGD2 also reduced ulcer formation, and considerable amounts of PGD2 in gastric mucosa were detected. 7. It can be concluded that H+ is a determining factor in the genesis of indomethacin-induced gastric ulcers and that persistent decreases in tissue PG levels also participate in ulcer formation.
Fukui
A
A
Department of Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
Nakazawa
S
S
Goto
H
H
Sugiyama
S
S
Ozawa
T
T
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D009853:Omeprazole / Q000627:therapeutic use*; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000188:drug therapy; D015230:Prostaglandin D2 / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D011453:Prostaglandins; D011451:Prostaglandin-Endoperoxide Synthases; D009853:Omeprazole; D015230:Prostaglandin D2; D007213:Indomethacin