Effect of selective and non-selective muscarinic blockade on baclofen inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.
The effects of baclofen, a gamma-amino-n-butyric acid receptor B agonist, on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine and how its effects are influenced by selective (M1) and non-selective (M1 and M2) pharmacological blockade of muscarinic receptors were investigated in inbred Wistar rats. Rats were given s.c. injections of 8 mg/kg body wt baclofen with and without 0.5 mg/kg body wt atropine (non-selective M1 and M2 muscarinic receptor antagonist) or 1.0 mg/kg body wt pirenzepine (selective M1 muscarinic receptor antagonist) every other day after a 25 week carcinogen treatment. At week 52 baclofen significantly decreased the incidence of gastric cancers. Concomitant treatment with atropine significantly attenuated the inhibition by baclofen of gastric carcinogenesis, but combined use with pirenzepine had no significant effect on the inhibition by baclofen of gastric carcinogenesis. Baclofen also significantly decreased the labeling index of the antral mucosa. Baclofen plus atropine attenuated the decrease in the labeling index of the antral mucosa due to baclofen, but baclofen plus pirenzepine had no significant effect on the labeling index. These results suggest that the inhibition of gastric carcinogenesis by baclofen is mediated through muscarinic receptors and M2 receptors, but not M1 receptors, are involved in this response.
Tatsuta
M
M
Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan.
Iishi
H
H
Baba
M
M
Yano
H
H
Uehara
H
H
Nakaizumi
A
A
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001418:Baclofen / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002273:Carcinogens; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D008769:Methylnitronitrosoguanidine; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D010890:Pirenzepine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D002273:Carcinogens; D018755:GABA Agonists; D018727:Muscarinic Antagonists; D008769:Methylnitronitrosoguanidine; D010890:Pirenzepine; D001285:Atropine; D001973:Bromodeoxyuridine; D001418:Baclofen