EFFECTS OF PROGLUMIDE AND ENPROSTIL ON OMEPRAZOLE-INDUCED FUNDIC ENDOCRINE CELL HYPERPLASIA IN RATS

Long-term treatment with omeprazole induces hyperplasia of enterochrom affin-like cells, closely related to hypergastrinemia. We studied whet her proglumide, an antagonist of gastrin/CCK receptor, and enprostil, a synthetic prostaglandin E2 derivative, might inhibit this hyperplasi a. Six groups of 8 rats were treated for 10 weeks: a) untreated contro ls; b) omeprazole 10 mumol/kg; c) proglumide 500 mg/kg; d) enprostil 3 0 mug/kg; e) association of omeprazole and proglumide; f) association of omeprazole and enprostil. Serum gastrin levels were measured at dif ferent times during treatment. After sacrifice, fundic argyrophil cell s were assessed by Grimelius' staining. Serum gastrin levels and argyr ophil cell density were not modified in proglumide- and enprostil-trea ted groups, as compared with controls. Omeprazole increased significan tly these two parameters. When given with omeprazole, proglumide decre ased significantly serum gastrin levels and argyrophil cell density, a s compared to omeprazole alone, while enprostil did not modify signifi cantly these two parameters. These results indicate that proglumide, b ut not enprostil, can counteract the omeprazole-induced argyrophil cel l hyperplasia in rats.