[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.
Kosaka
N
N
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo, Co., Ltd., Shizuoka, Japan.
Tanaka
H
H
Ishii
A
A
Shuto
K
K
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