Helicobacter pylori induces pepsinogen secretion by rat gastric cells in culture via a cAMP signal pathway

Infection with Helicobater pylori (H. pylori) is associated with various st omach diseases such as chronic gastritis, peptic ulcer, and gastric carcino ma. In order to investigate the mechanisms of enhanced production of pepsin ogen by H. pylori in cultured rat gastric cells that have the potential to produce pepsinogen, secretion and synthesis of pepsinogen in the cells expo sed to H. pylori extract were determined by measuring the hydrolysis of hem oglobin. Various drugs were used to study the mechanisms of effects of H. p ylori on the cells. Exposure of the gastric cells to H. pylori extract caus ed a significant increase in pepsinogen secretion into the culture medium w ithin 30-180 min in a dose-dependent manner, accompanied by a significant i ncrease in pepsinogen synthesis in the gastric cells after 60 min of incuba tion. Heat treatment of the H. pylori sonicate at 100 degreesC for 10 min c ompletely abolished the stimulatory effect of H. pylori on pepsinogen secre tion. 2(1),3(1)-Dideoxyadenosine (50 muM), a specific adenylate cyclase inh ibitor, abolished the effect of H. pylori-induced pepsinogen secretion. Pur omycin (10 mug/ml), a protein synthesis inhibitor, and nicorandil (0.1 mM), a specific intracellular calcium antagonist, reduced the H, pylori-induced pepsinogen secretion by 37% (p <0.01) and 25% (p <0.05), respectively. On the other hand, actinomycin D (1 mug/ml), an RNA synthesis inhibitor, did n ot affect the H. pylori-induced pepsinogen secretion. Consequently, dibutyr yl cAMP potentially stimulated the pepsinogen secretion from gastric epithe lial cells in a dose-dependent manner. H. pylori induces pepsinogen secreti on and synthesis by gastric epithelial cells through an increase in the int racellular cAMP and mobilization of the intracellular calcium. In addition, H. pylori affects pepsinogen synthesis at the translational level.