EFFECTS OF LONG-TERM OMEPRAZOLE TREATMENT ON ADULT-RAT GASTRIC-MUCOSA- ENHANCEMENT OF THE EPITHELIAL-CELL PROLIFERATION AND SUPPRESSION OFITS DIFFERENTIATION

Effects of long-term omeprazole treatment on the process of epithelial cell proliferation and differentiation in the adult rat gastric mucos a were investigated. Animals were treated with omeprazole (25 mg/kg bo dy weight/day) for 28 days to induce anacidity in the stomach. The tre atment induced a marked decrease in the number of chief cells in the g astric mucosa and at the same time an increase in that of immature pep sinogen-producing cells expressing class III mucin. This was accompani ed by a decrease to 60% and 10% of the control values in the mucosal l evels of pepsinogen and its mRNA, respectively. Moreover, the expressi on of cathepsin E in surface mucous cells was reduced. Cell proliferat ion studies revealed that the rate of bromodeoxyuridine-labeled cells was increased by omeprazole. The above-described changes were reversed by cessation of the treatment and they were not caused by the omepraz ole-treatment at a dose which does not induce anacidity in the stomach . These results suggest that long-term omeprazole treatment reversibly increases the epithelial cell proliferation and suppresses its differ entiation in the adult rat gastric mucosa probably by altering the aci dic environment specific for the stomach. (C) 1995 Academic Press, Inc .