Effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711), a new anti-ulcer agent, on gastric mucosal lesions induced by necrotizing agents and gastric mucosal defensive factors in rats.
Effects of TA-2711 on gastric mucosal lesions induced by various necrotizing agents and several defensive factors of gastric mucosa were investigated in rats. Oral administration of TA-2711 at 12.5 to 200 mg/kg prevented the formation of gastric mucosal lesions induced by 99.5% ethanol, 0.6 N HCl, 0.2 N NaOH and boiling water with ED50 values of 24, 58, 16 and 101 mg/kg, respectively. Oral TA-2711 at 100 mg/kg increased the gastric mucosal prostaglandin E2 (PGE2) level without any change in transmucosal potential difference. A sustained decrease in gastric mucosal blood flow produced by intragastric administration of 99.5% ethanol was inhibited by oral TA-2711 (50, 100 mg/kg) and 16,16-dimethyl PGE2 (10 micrograms/kg). The effect of TA-2711 on ethanol-induced decrease in blood flow was suppressed by indomethacin (10 mg/kg, s.c.). Oral TA-2711 (25-100 mg/kg) dose-dependently increased the amount of mucus adherent to the gastric mucosa. In addition, gastric HCO3- secretion was increased by intragastric TA-2711 at 2.5 and 5.0 mg/ml. These results suggest that TA-2711 enhances gastric mucosal resistance by increasing mucus and HCO3- secretion and by maintaining mucosal blood flow, and protects the gastric mucosa against various irritants. The effects of TA-2711 appear to be mediated by mucosal prostaglandins such as PGE2.
Onoda
Y
Y
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Takido
M
M
Magaribuchi
T
T
Tamaki
H
H
D045784:Abietanes; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009093:Mucus / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D013392:Sucralfate / Q000494:pharmacology; D014148:Tranexamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D045784:Abietanes; D000897:Anti-Ulcer Agents; D004224:Diterpenes; C061681:ecabet; D013392:Sucralfate; C000665:cetraxate; D014148:Tranexamic Acid; D015232:Dinoprostone