ROLE OF LUMINAL AMMONIA IN THE DEVELOPMENT OF GASTROPATHY AND HYPERGASTRINEMIA IN THE RAT

Background/Aims: Chronic infection with Helicobacter pylori causes per sistent elevations in gastric juice ammonia levels. Thus, we studied t he effects of experimentally induced increases in gastric juice ammoni a levels on gastric structure and function and gastrin homeostasis. Me thods: Rats were fed either normal chow or the diet supplemented (20 g /dL) with ammonium or sodium acetate. Results: Long-term dietary ammon ium loading for 2 weeks or longer resulted in a 1.5-2-fold increase in the weight and mucosal thickness of the stomach and proximal duodenum with evidence of mild gastritis and enterochromaffinlike cell hyperpl asia. The ammonium-containing diet also induced a significant 2-3-fold increase in both circulating gastrin levels of fed rats and an increa se in the postprandial gastrin responses over control values. Antral g astrin levels were also markedly elevated by longterm ingestion of the test diet, which was increased 3-4-fold over control values in fasted animals and less so after meal stimulation. Consistent with these fin dings, gastrin-specific messenger RNA was increased 2.5-3-fold in the antrum of ammonium fed rats, whereas actin-specific messenger RNA was not affected or decreased. Animals fed a diet supplemented with 20 g/d L sodium acetate sustained modest increases in mucosal thickness and s erum and antral gastrin concentration, suggesting that nonspecific gas tric injury and inflammation is also a factor that influences G-cell f unction. Conclusions: Long-term exposure of the antral mucosa to eleva ted levels of ammonia in the gastric juice in the presence of gastriti s, conditions similar to that occurring in subjects infected with H. p ylori, seem to be causative factors in the development of G-cell hyper function.