Effect of FRG-8813, a new histamine H2-receptor antagonist, on gastric mucus production in rats

Abstract

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.