[Effect of 5-[2-(diethylamino)ethyl]amino-5,11- dihydro[1]benzoxepino[3,4-b]pyridine trihydrochloride (KW-5805) on the biosynthesis of rat gastric mucus].
The effect of 5-[2-(diethylamino)ethyl]amino-5,11- dihydro[1]benzoxepino[3,4-b]pyridine trihydrochloride (KW-5805) on the activity of an enzyme regulating gastric mucous aminosugar metabolism was studied in rats. Restraint and water-immersion stress decreased the gastric mucosal glucosamine synthetase activity and induced gastric ulcers. The decrease of the enzyme activity reached a maximum at 1 hr and then returned to the non-stressed value. Pretreatment with KW-5805 at oral doses of 3 and 30 mg/kg inhibited the decrease of the enzyme activity and the gastric adherent mucus content and gastric ulceration induced by the stress. KW-5805 (30 mg/kg, p.o.) increased the enzyme activity in normal rats and also prevented the decrease of gastric mucosal N-acethylglucosamine kinase activity in the stressed rats. KW-5805 stimulated the activities of gastric mucosal. UDP-N-acethylglucosamine 4-epimerase and UDP-galactosyltransferase in in vitro. These results suggested that the antiulcerogenic effect of KW-5805 might be due to the activation of an enzyme regulating the biosynthesis of gastric mucus resulting in the reinforcement of gastric mucosal defensive mechanisms.
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo, Co., Ltd., Shizuoka, Japan.
N
N
Kosaka
H
H
Tanaka
A
A
Ishii
K
K
Shuto
D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001584:Benzoxepins / Q000008:administration & dosage / Q000494:pharmacology*; D002238:Carbohydrate Epimerases / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000378:metabolism; D007101:Immersion; D066298:In Vitro Techniques; D009093:Mucus / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000378:metabolism
D000897:Anti-Ulcer Agents; D001584:Benzoxepins; C055432:KW 5805; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); D017853:Phosphotransferases (Alcohol Group Acceptor); C018716:N-acetylglucosamine kinase; D002238:Carbohydrate Epimerases; C023223:UDP-N-acetylglucosamine 4-epimerase