Kagoshima M, Kodaira H, Tanaka M, Shimada H
Department of Clinical Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Nihon Yakurigaku Zasshi. 1995 Dec;106(6):385-92. doi: 10.1254/fpj.106.385.
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.
我们研究了新型组胺H2受体拮抗剂FRG - 8813对1%氨诱导的大鼠胃黏膜损伤及基础胃黏液分泌的影响。将口服给予的FRG - 8813（10毫克/千克）的作用与16,16 - 二甲基前列腺素E2（dmPGE2，2微克/千克）或辣椒素（Cap，10毫克/千克）在胃底腺区域的作用进行了宏观和组织化学比较。FRG - 8813、dmPGE2和辣椒素均能抑制氨诱导的黏膜损伤，并在给药后5分钟刺激黏液分泌。化学去传入神经作用消除了FRG - 8813或辣椒素的胃保护作用，并减弱了FRG - 8813、dmPGE2或辣椒素在5分钟后所见的黏液分泌增加。这些结果表明，FRG - 8813对胃黏液分泌的作用部分是通过辣椒素敏感的传入神经介导的，类似于胃保护作用的机制，并且FRG - 8813引起的黏液分泌增加至少部分地促成了胃保护作用。
