Basic-alimentary tractSynergistic Inhibitory Effects of Gastrin and Histamine Receptor Antagonists on Helicobacter-Induced Gastric Cancer
Section snippets
Animals
The INS-GAS transgenic mice (FVB/N background) have been described previously7, 21 and were free of specific murine pathogens. Animals were housed in microisolator, solid-bottomed polycarbonate cages, fed a commercially prepared pelleted diet, and given water ad libitum. A total of 124 male INS-GAS mice at 2 or 3 months of age were inoculated with H felis (ATCC 49179) 3 times every other day in 1 week with a dose of about 1 billion colony-forming units per mouse each time.7 Infection status was
YF476 and/or Loxtidine Treatment for 3 Months Resulted in Synergistic Inhibition of Gastric Acid Output and Gastric Atrophy, Hyperplasia, and Dysplasia in H felis-Infected INS-GAS Mice
While the highly specific CCK2/gastrin receptor antagonist YF476 and the irreversible histamine H2-receptor antagonist loxtidine have previously been shown to inhibit acid secretion in mice, they have not been studied in models of chronic Helicobacter infection. In addition, they have not previously been examined in a mouse model of gastric cancer such as the hypergastrinemic INS-GAS mouse model. Previous studies have shown that young (<6 months of age) INS-GAS mice have substantially elevated
Discussion
In this study, we have investigated in our H felis-infected INS-GAS mouse model the effect of 3 distinct acid-suppressive reagents: the CCK2/gastrin receptor antagonist YF476, the histamine H2-receptor antagonist loxtidine, and the PPI omeprazole. All 3 drugs strongly inhibit gastric acid secretion and were initially developed as antiulcer or anti-gastroesophageal reflux disease drugs. Our results strongly suggest that the gastrin-histamine axis contributes to the development of gastric atrophy
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G.C.’s current affiliation is: Laboratory of Gastroenterology, University of Tromso, Tromso, Norway.
Supported in part by National Institutes of Health grants CA93405 and DK48077 (to T.C.W) and AI37750 and RR07036 (to J.G.F.).