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.
Campbell
V W
VW
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0682.
Yamada
T
T
D000199:Actins / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000818:Animals; D015152:Blotting, Northern; D002256:Carbonic Anhydrases / Q000235:genetics*; D015342:DNA Probes; D004285:Dogs; D015870:Gene Expression / Q000187:drug effects; D017506:H(+)-K(+)-Exchanging ATPase; D066298:In Vitro Techniques; D007700:Kinetics; D009693:Nucleic Acid Hybridization; D009853:Omeprazole / Q000494:pharmacology*; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification
D000199:Actins; D015342:DNA Probes; D012333:RNA, Messenger; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D002256:Carbonic Anhydrases; D009853:Omeprazole