enprostil and Hyperplasia

Long-term treatment with omeprazole induces hyperplasia of enterochromaffin-like cells, closely related to hypergastrinemia. We studied whether proglumide, an antagonist of gastrin/CCK receptor, and enprostil, a synthetic prostaglandin E2 derivative, might inhibit this hyperplasia. Six groups of 8 rats were treated for 10 weeks: a) untreated controls; b) omeprazole 10 mumol/kg; c) proglumide 500 mg/kg; d) enprostil 30 micrograms/kg; e) association of omeprazole and proglumide; f) association of omeprazole and enprostil. Serum gastrin levels were measured at different times during treatment. After sacrifice, fundic argyrophil cells were assessed by Grimelius' staining. Serum gastrin levels and argyrophil cell density were not modified in proglumide- and enprostil-treated groups, as compared with controls. Omeprazole increased significantly these two parameters. When given with omeprazole, proglumide decreased significantly serum gastrin levels and argyrophil cell density, as compared to omeprazole alone, while enprostil did not modify significantly these two parameters. These results indicate that proglumide, but not enprostil, can counteract the omeprazole-induced argyrophil cell hyperplasia in rats.

Topics: Animals; Cell Count; Depression, Chemical; Drug Combinations; Enprostil; Enterochromaffin Cells; Female; Gastric Fundus; Gastrins; Hyperplasia; Omeprazole; Proglumide; Rats; Rats, Wistar; Reference Values

A 42-year-old man with a 26-year history of duodenal ulcer volunteered for a 24-hour intragastric pH monitoring study, at which time his fasting gastrin concentration was found to be elevated. Secretin injection decreased the serum gastrin concentration. When not on treatment his total gastrin, gastrin-17 (G-17), and gastrin-34 (G-34) response to a protein-containing breakfast was marked. Immunocytochemical staining of antral biopsies showed hyperplasia of gastrin-containing cells, more pronounced for G-17 than for G-34. Cimetidine or cimetidine plus pirenzepine increased 24-hour intragastric pH, whereas pirenzepine alone rendered the gastric contents more acidic, particularly overnight. The total serum gastrin concentrations increased after meals and were unaffected by cimetidine or pirenzepine; enprostil, however, reduced the postprandial increase in total gastrin, G-34, and G-17. After six weeks of treatment with enprostil, the number of cells containing G-17 and G-34 was reduced. The findings show that G-cell hyperplasia may occur in the presence of a normal fasting serum gastrin concentration; fasting serum gastrin concentrations may fluctuate widely over time; the food-stimulated increase in G-17 was greater than that for G-34, and is associated with more pronounced antral hyperplasia for G-17 and G-34; and enprostil blunts the postprandial increase in G-17, G-34, and total gastrin. These observations suggest that enprostil may reduce G-cell hyperplasia and hypergastrinemia.

Topics: Adult; Cimetidine; Duodenal Ulcer; Enprostil; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Hyperplasia; Male; Pirenzepine; Prostaglandins E, Synthetic; Pyloric Antrum