EFFECT OF OMEPRAZOLE ON GENE-EXPRESSION IN CANINE GASTRIC PARIETAL-CELLS

Stimulation of gastric parietal cells by carbachol induces coordinate expression of the genes for two enzymes involved in the process of acid secretion, H+-K+-ATPase and carbonic anhydrase II (CA II). The basis of this coordinate expression was examined in experiments using parietal cells that had been pretreated with omeprazole. We observed a twofold increase in the steady-state mRNA levels of both H+-K+-ATPase and CA II after cells were treated with the inhibitor. The induction of CA II mRNA by carbachol followed the same kinetics in omeprazole-pretreated cells as in those that were not pretreated, suggesting that the induction of CA II gene expression by carbachol was not dependent on activation of the gastric H+-K+-ATPase. In addition, carbachol stimulation of omeprazole-pretreated cells resulted in an induction of one or more larger mRNA species that hybridized with the H+-K+-ATPase probe. The observation that carbachol-induced increases in steady-state levels of beta-actin mRNA in parietal cells could be inhibited by omeprazole pretreatment suggests a possible linkage between increased beta-actin gene expression and the process of acid secretion.