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The Gastrin Receptor Antagonist Netazepide (YF476) Prevents Oxyntic Mucosal Inflammation Induced by Helicobacter Pylori Infection in Mongolian Gerbils

Authors

  • Øystein Sørdal,

    Corresponding author
    1. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
    • Reprint requests to: Øystein Sørdal, Department of Cancer Research and Molecular Medicine at the Norwegian University of Science and Technology, Trondheim, Norway. E-mail: osordal@rcsi.ie

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  • Helge Waldum,

    1. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
    2. Department of Gastroenterology and Hepatology, St.Olav's University Hospital, Trondheim, Norway
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  • Ivar S. Nordrum,

    1. Department of Pathology and Medical Genetics, St Olav's University Hospital, Trondheim, Norway
    2. Department of Laboratory Medicine, Children and Woman Health, NTNU, Trondheim, Norway
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  • Malcolm Boyce,

    1. Hammersmith Medicines Research, London, UK
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  • Kåre Bergh,

    1. Department of Laboratory Medicine, Children and Woman Health, NTNU, Trondheim, Norway
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  • Bjørn Munkvold,

    1. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
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  • Gunnar Qvigstad

    1. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
    2. Department of Gastroenterology and Hepatology, St.Olav's University Hospital, Trondheim, Norway
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Abstract

Objective

Long-term Helicobacter pylori infection causes gastritis leading to hypergastrinemia and predisposes to gastric cancer. Our aim was to assess the role of gastrin in oxyntic mucosal inflammation in H. pylori-infected Mongolian gerbils by means of the gastrin receptor antagonist netazepide (YF476).

Design

We studied 60 gerbils for 18 months and left five animals uninfected (control group), inoculated 55 with H. pylori, and treated 28 of the infected animals with netazepide (Hp+YF476 group). Twenty-seven infected animals were given no treatment (Hp group). We measured plasma gastrin and intraluminal pH. H. pylori detection and histologic evaluations of the stomach were carried out.

Results

All 55 inoculated animals were H. pylori positive at termination. Eighteen animals in the Hp group had gastritis. There was a threefold increase in mucosal thickness in the Hp group compared to the Hp+YF476 group, and a threefold increase in oxyntic neuroendocrine cells in the Hp group compared to the Hp+YF476 group (p < .05). All animals in the Hp+YF476 group had macro- and microscopically normal findings in the stomach. Plasma gastrin was higher in the Hp group than in the control group (172 ± 16 pmol/L vs 124 ± 5 pmol/L, p < .05) and highest in the Hp+YF476 group (530 ± 36 pmol/L). Intraluminal pH was higher in the Hp group than in the Hp+YF476 group (2.51 vs 2.30, p < .05).

Conclusion

The gastrin antagonist netazepide prevents Hpylori-induced gastritis in Mongolian gerbils. Thus, gastrin has a key role in the inflammatory reaction of the gastric mucosa to Hpylori infection in this species.

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