The gastrin receptor antagonist netazepide (YF476) prevents oxyntic mucosal inflammation induced by Helicobacter pylori infection in Mongolian gerbils.

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).
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.
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).
The gastrin antagonist netazepide prevents H. pylori-induced gastritis in Mongolian gerbils. Thus, gastrin has a key role in the inflammatory reaction of the gastric mucosa to H. pylori infection in this species.
AuthorsØystein Sørdal, Helge Waldum, Ivar S Nordrum, Malcolm Boyce, Kåre Bergh, Bjørn Munkvold, Gunnar Qvigstad
JournalHelicobacter (Helicobacter) Vol. 18 Issue 6 Pg. 397-405 (Dec 2013) ISSN: 1523-5378 [Electronic] England
PMID23865485 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013 John Wiley & Sons Ltd.
Chemical References
  • Benzodiazepinones
  • Phenylurea Compounds
  • Receptor, Cholecystokinin B
  • YF 476
  • Animals
  • Benzodiazepinones (administration & dosage)
  • Disease Models, Animal
  • Gastric Mucosa (drug effects, immunology, microbiology)
  • Gerbillinae
  • Helicobacter Infections (drug therapy, immunology, microbiology, prevention & control)
  • Helicobacter pylori (drug effects, physiology)
  • Humans
  • Male
  • Phenylurea Compounds (administration & dosage)
  • Receptor, Cholecystokinin B (antagonists & inhibitors, immunology)

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