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

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 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.

• Authors: Øystein Sørdal, Helge Waldum, Ivar S Nordrum, Malcolm Boyce, Kåre Bergh, Bjørn Munkvold, Gunnar Qvigstad
• Journal: Helicobacter (Helicobacter) Vol. 18 Issue 6 Pg. 397-405 (Dec 2013) ISSN: 1523-5378 [Electronic] England
• PMID: 23865485 (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

Topics

• 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)