Role of Thromboxane A_2 in Healing of Gastric Ulcers in Rats
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概要
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We investigated the role of thromboxane (TX) A2 in gastric ulcer healing in rats. Acetic acid ulcers were produced in male Donryu rats. TXA2 synthesis in the stomachs with ulcers was significantly elevated in ulcerated tissue, but not in intact tissue, compared with that in the gastric mucosa of normal rats. Indomethacin inhibited both TXA2 and prostaglandin E2 (PGE2) synthesis in ulcerated tissue, while NS-398 (selective cyclooxygenase-2 inhibitor) reduced only PGE2 synthesis. OKY-046 (TXA2 synthase inhibitor) dose-relatedly inhibited only TXA2 synthesis. The maximal effect of OKY-046 (80% inhibition) was found at more than 30 mg/kg. When OKY-046 was administered for 14 days, the drug at more than 30 mg/kg significantly accelerated ulcer healing without affecting acid secretion. The maximal reduction of ulcerated area by OKY-046 was about 30%, compared with the area in the control. Histological studies revealed that regeneration of the mucosa was significantly promoted by OKY-046, but neither maturation of the ulcer base nor angiogenesis in the base were affected. OKY-046 and TXB2 had no effect on proliferation of cultured rat gastric epithelial cells, but U-46619 (TXA2 mimetic) dose-relatedly prevented the proliferation without reducing cell viability. These results indicate that the increased TXA2, probably derived from cyclooxygenase-1 in ulcerated tissue, exerts a weak inhibitory effect on ulcer healing in rats. The effect of TXA2 might be due partly to prevention of gastric epithelial cell proliferation at the ulcer margin.
- 社団法人 日本薬理学会の論文
著者
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Ishikawa Makoto
Department of Cardiology, Fujita Health University
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Okabe Susumu
Department Of Applied Pharmacology Kyoto College Of Pharmacy
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Takahashi Satoru
Department Of Anatomy And Embryology Biomolecular And Integrated Medical Sciences Graduate School Of
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SHIGETA Jun-ichi
Department of Applied Pharmacology, Kyoto Pharmaceutical University
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KOBAYASHI Norihiro
Department of Applied Pharmacology, Kyoto Pharmaceutical University
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Shigeta Jun-ichi
Department Of Applied Pharmacology Kyoto Pharmaceutical University
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Kobayashi Norihiro
Department Of Applied Pharmacology Kyoto Pharmaceutical University
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Ishikawa Makoto
Department Of Applied Chemistry Keio University
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Takahashi Satoru
Department Of Applied Pharmacology Kyoto Pharmaceutical University
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