Omeprazole, a proton pump inhibitor, reduces the secretion, synthesis and gene expression of pepsinogen in the rat stomach.

Omeprazole, a proton pump inhibitor, dose-dependently inhibited pepsinogen secretion as well as acid secretion in the rat glandular stomach. The reduction in the secretion was rapid and was followed by a decrease in the mRNA levels. The inhibitory effect of omeprazole on pepsinogen secretion and its effect on the mRNA level showed similar dose-response relationship, suggesting that pepsinogen secretion and the gene expression are regulated coordinately. Consistent with the reduction in the mRNA levels, protein synthesis was reduced. However, intracellular stores of pepsinogen increased in pepsinogen-producing cells, indicating that the inhibitory effect of omeprazole on pepsinogen secretion is greater than on its synthesis. Reducing the secretion, synthesis and gene expression of pepsinogen, omeprazole has a potent effect on pepsinogen-producing cells in vivo, as well as on parietal cells, in the rat glandular stomach.