[Effect of FRG-8813, a new histamine H2-receptor antagonist, on gastric mucus production in rats].
We examined the effect of FRG-8813, a new histamine H2-receptor antagonist, on 1% NH3-induced gastric mucosal lesions and basal gastric mucus production in rats. The effect of FRG-8813 (10 mg/kg) given orally was investigated macroscopically and histochemically compared with that of 16,16-dimethyl prostaglandin E2 (dmPGE2, 2 micrograms/kg) or capsaicin (Cap, 10 mg/kg) in the fundic gland area. FRG-8813, dmPGE2 and capsaicin inhibited the NH3-induced mucosal lesions, and stimulated the mucus secretion 5 min after the administration. Chemical deafferentation abolished the gastroprotective effect of FRG-8813 or Cap and attenuated the increase by FRG-8813, dmPGE2 or Cap in mucus secretion seen after 5 min. These results suggest that FRG-8813 exerts its effect on gastric mucus production partially through the capsaicin-sensitive afferent nerves, like the mechanism involved in gastroprotection, and that the increase in mucus production by FRG-8813 is at least in part responsible for the gastroprotection.
Kagoshima
M
M
Department of Clinical Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Kodaira
H
H
Tanaka
M
M
Shimada
H
H
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D009093:Mucus / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000081:Acetamides; D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D010880:Piperidines; D011725:Pyridines; C076948:lafutidine; D015064:16,16-Dimethylprostaglandin E2; D002211:Capsaicin