A review of the effects of long-term acid inhibition in animals.
Studies with H2-receptor antagonists have revealed a trophic effect on the gastric mucosa - an effect which has been ascribed to hypergastrinaemia secondary to acid inhibition. Such hyperplasia of oxyntic mucosal cells has also been demonstrated in chronic toxicity studies following profound, long-standing inhibition of gastric acid secretion with omeprazole. The central role of gastrin in this effect was clearly demonstrated in the omeprazole studies, as antrectomy prevented this effect in both rats and dogs. The hyperplasia was fully reversible in both species. The close correlation between serum gastrin and hyperplasia of enterochromaffin-like (ECL) cells in the rat oxyntic mucosa has been demonstrated in a large number of experiments using different means to induce hypergastrinaemia, including administration of exogenous gastrin, treatment with antisecretory drugs and partial fundectomy. The hyperplasia of ECL cells was fully reversible even after 1 year of sustained gastric acid inhibition following treatment with a high dose of omeprazole. Marked long-standing hypergastrinaemia explains the findings of gastric ECL cell carcinoids in the life-long rat toxicity studies with both omeprazole and other inhibitors of gastric acid secretion.
Carlsson
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Gastrointestinal Research, AB Hässle, Mölndal, Sweden.
D000818:Animals; D004759:Enterochromaffin Cells / Q000187:drug effects; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects*; D005755:Gastrins / Q000097:blood*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008134:Long-Term Care; D009853:Omeprazole / Q000494:pharmacology*
D005755:Gastrins; D006635:Histamine H2 Antagonists; D009853:Omeprazole