[Effects of FRG-8813, a new histamine H2-receptor antagonist, on gastric mucus in rats].
We examined the effects of FRG-8813, a new histamine H2-receptor antagonist with potent antisecretory activity, on gastric mucus in male SD rats (7w). In this study, the effects of FRG-8813 (1, 3, 10 mg/kg), given orally twice a day for 7 days, were investigated by histochemical and biochemical methods in comparison with those of cimetidine (CM, 30 mg/kg) and famotidine (FM, 1 mg/kg) in the fundic gland area (F. area) and pyloric gland area (P. area). In the histochemical study by alcian blue (pH 2.5)-PAS (AB-PAS) or high iron diamine-alcian blue (HID-AB) staining, the CM group showed a significant decrease in PAS and tended to show decreases in HID-AB positive mucus and mucous gel layer in the F. area; the FM group also showed a decrease in AB positive mucus in the P. area. On the other hand, the AB-PAS and HID-AB positive mucus of the FRG-8813 group were not affected. In the biochemical study, FRG-8813 increased the gastric mucosal hexose, hexosamine and sialic acid composing the mucus in a dose-dependent manner in the F. area. These results suggest that FRG-8813 does not cause a decrease in gastric mucus, unlike CM or FM, and it may be able to promote mucus secretion through increasing the mucous component in the F. area.
Kagoshima
M
M
Department of Clinical Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Kodaira
H
H
Shimada
H
H
D000081:Acetamides / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015738:Famotidine / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism*; D006601:Hexoses / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009093:Mucus / Q000378:metabolism*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000081:Acetamides; D006601:Hexoses; D006635:Histamine H2 Antagonists; D010880:Piperidines; D011725:Pyridines; C076948:lafutidine; D015738:Famotidine; D002927:Cimetidine