Inhibition by gamma-amino-n-butyric acid and baclofen of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.
The effect of gamma-amino-n-butyric acid (GABA), the GABA(A) receptor agonist muscimol (5-aminomethyl-3-hydroxyisoxazole), and the GABA(B) receptor agonist baclofen [4-amino-3-(4-chlorophenyl)butanoic acid] on the incidence and number of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine was investigated in Wistar rats. Rats received alternate-day i.p. injections of 500 or 1000 mg/kg of body weight GABA, 0.25 or 0.5 mg/kg of body weight muscimol, or 4 or 8 mg/kg of body weight baclofen after 25 wk of p.o. treatment with the carcinogen. Prolonged administration of GABA at 1000 mg/kg of body weight, but not at 500 mg/kg of body weight, and of baclofen at 4 and 8 mg/kg of body weight significantly decreased the incidence and number of gastric cancers of the glandular stomach in Wk 52, but long-term muscimol administration had no influence. Histologically, GABA at the high dosage and baclofen at both dosages significantly decreased the labeling index of the antral mucosa and significantly increased the serum gastrin level. Furthermore, baclofen at both dosages significantly decreased antral pH and significantly increased gastric acid secretion. These findings indicate that GABA inhibits gastric carcinogenesis via the GABAB receptor and that this effect may be related to its effect in decreasing the proliferation of antral mucosa.
Tatsuta
M
M
Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan.
Iishi
H
H
Baba
M
M
Nakaizumi
A
A
Ichii
M
M
Taniguchi
H
H
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D008769:Methylnitronitrosoguanidine; D005680:gamma-Aminobutyric Acid; D001418:Baclofen