Alimentary TractRegenerating gene protein may mediate gastric mucosal proliferation induced by hypergastrinemia in rats☆,☆☆
Section snippets
Effect of chronic hypergastrinemia on rat stomach
Seven-week-old male Sprague–Dawley rats (Clea Japan, Tokyo, Japan) were divided into four groups. The first group received the vehicle, 0.5% sodium carboxymethyl cellulose, pH 7.6, via a gastric tube once a day for 28 days. The second group was treated with lansoprazole (Takeda, Osaka, Japan) diluted in the vehicle, at a dose of 30 mg/kg body wt once a day for 28 days. This dose has been shown to induce complete achlorhydria in adult rats.16 The third group was treated with both the gastrin
Effects of long-term administration of lansoprazole and/or the gastrin receptor antagonist on rat stomach
In rats given lansoprazole or AG-041R, the serum gastrin level was increased significantly (P < 0.01 and P < 0.05, respectively, vs. control). Concomitant administration of lansoprazole and AG-041R further increased the serum gastrin level (P < 0.01) (Table 1).
The thickness of the fundic mucosa in control rats was 509 ± 4 μm and was significantly increased by lansoprazole administration (P < 0.01). The effect of lansoprazole on the mucosal thickness was completely abolished by concomitant
Discussion
In the present study, we have clearly shown that chronic hypergastrinemia induced by lansoprazole enhanced the proliferation of gastric mucosal cells, particularly in the neck zone, and increased the thickness of the fundic mucosa in rats. This trophic action was completely abolished by a potent gastrin receptor antagonist, AG-041R. These data agree well with the results of several previous in vivo studies showing that chronic hypergastrinemia exerts a trophic action on the gastric mucosa6, 7,
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Address requests for reprints to: Tsutomu Chiba, M.D., Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54, Kawaramachi-shogoin, Sakyo-ku, Kyoto 606-01, Japan. Fax: (81) 75-751-4303.
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Supported in part by Grants-in-aid for Scientific Research and Cancer Research from the Ministry of Education, Science and Culture, a grant from the Ministry of Health and Welfare, Japan, and from the Japan Society for the Promotion of Science (no. JSPS-RFTF97I00201).