Acid secretagogue-induced stimulation of gastric parietal cell gene expression

Carbamoylcholine (carbachol), histamine, and gastrin are three principal stimulants of gastric acid secretion. To explore the mechanisms by which these agents exert their actions in parietal cells, we examined their effects on the gene expression of the enzymes responsible for H+ generation. Each secretagogue induced rapid and coordinate increases in steady-state levels of mRNAs encoding carbonic anhydrase II and H+,K+-ATPase in isolated canine gastric parietal cells. Furthermore, pronounced increases, with different kinetics, in expression of beta-actin mRNA were observed. With increasing time after cell isolation, carbonic anhydrase II and H+,K+-ATPase, but not beta-actin, mRNA levels were attenuated, suggesting that parietal cell-specific genes may be dependent upon maintenance of parietal cell contacts within intact mucosal tissue. Pretreatment of the cells with competitive inhibitors of each secretagogue blocked the increases. Our results indicate that acid secretagogue-specific receptor activation in parietal cells triggers coordinate gene expression of the two enzymes involved in H+ ion generation and that beta-actin may be an important regulator of acid secretion.