[Effect of KW-5805 on gastric mucus changes induced by water immersion-restraint stress and aspirin in rats].
The effects of 5-[2-(diethylamino)ethyl]amino-5,11-dihydro[1]benzoxepino[3,4- b]pyridine trihydrochloride (KW-5805) on the changes of gastric mucus induced by stress and aspirin were studied in rats. Water immersion-restraint stress time-dependently decreased the gastric adherent mucus content and induced gastric ulcers. Aspirin, administered orally at 200 mg/kg, reduced the gastric adherent mucus level and produced gastric erosions. The diminution of gastric mucus reached a maximum at 3 hr, and a gradual return to the non-treatment value was observed subsequently. Pretreatment with KW-5805, given orally at 3, 10 or 30 mg/kg, dose-dependently prevented stress- and aspirin-induced mucus depletion and gastric ulceration. Gastric mucus glycoprotein levels, indicated by the contents of hexose and hexosamine, were also decreased by aspirin. KW-5805 pretreatment (30 mg/kg, p.o.) significantly inhibited the diminution of mucus glycoproteins. KW-5805 also increased the gastric adherent mucus content and the amount of glycoproteins in normal rats. These results suggested that the stimulating effects of KW-5805 on the secretion and storage of gastric mucus may account for some of its antiulcer properties.
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo, Co., Ltd., Shizuoka, Japan.
N
N
Kosaka
H
H
Tanaka
A
A
Ishii
K
K
Shuto
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001241:Aspirin / Q000009:adverse effects; D001584:Benzoxepins / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D007101:Immersion; D009093:Mucus / Q000378:metabolism*; D051381:Rats; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D013312:Stress, Physiological / Q000378:metabolism*
D000897:Anti-Ulcer Agents; D001584:Benzoxepins; D006023:Glycoproteins; C055432:KW 5805; D001241:Aspirin