Role of luminal ammonia in the development of gastropathy and hypergastrinemia in the rat

Abstract

$\text{Background/Aims}\text{:}$ Chronic infection with Helicobacter pylori causes persistent elevations in gastric juice ammonia levels. Thus, we studied the effects of experimentally induced increases in gastric juice ammonia levels on gastric structure and function and gastrin homeostasis. $\text{Methods}\text{:}$ Rats were fed either normal chow or the diet supplemented (20 g/dL) with ammonium or sodium acetate. $\text{Results}\text{:}$ Long-term dietary ammonium 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 hyperplasia. The ammonium-containing diet also induced a significant 2–3-fold increase in both circulating gastrin levels of fed rats and an increase in the postprandial gastrin responses over control values. Antral gastrin levels were also markedly elevated by long-term 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 findings, 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/dL sodium acetate sustained modest increases in mucosal thickness and serum and antral gastrin concentration, suggesting that nonspecific gastric injury and inflammation is also a factor that influences G-cell function. $\text{Conclusions}\text{:}$ Long-term exposure of the antral mucosa to elevated levels of ammonia in the gastric juice in the presence of gastritis, conditions similar to that occurring in subjects infected with H. pylori, seem to be causative factors in the development of G-cell hyperfunction.