Consumption of coffee beverages has been reported to cause gastric irritation in some consumers as a result of increased gastric acid secretion. In the complex mechanisms of gastric acid secretion, the activity and expression of the H+,K+-ATPase is regulated by transmitters, such as histamine, acetylcholine, gastrin, somatostatin, and their corresponding receptors. Here, we report the effect of three coffee constituents, chlorogenic acid, caffeine, and N-methyl pyridinium ions, on the expression of the histamine receptor H2, the acetylcholine receptor M3, the gastrin receptor, the somatostatin receptor, and the H+,K+-ATPase. Human gastric cancer cells were exposed to chlorogenic acid, caffeine, or N-methyl pyridinium in their coffee brew-representative concentrations as well as to physiological stimulators of gastric acid secretion. Gene expression levels of receptor proteins and those of the H+,K+-ATPase were measured at different time points by real-time PCR. Expression of prosecretory receptors significantly increased between one and one-half to twofold after treatment with chlorogenic acid or caffeine compared to control cells at the same time point. Chlorogenic acid and caffeine also increased the H+,K+-ATPase gene expression twofold higher compared to control cells. In contrast, N-methyl pyridinium downregulated the expression of the prosecretory gastrin receptor significantly, by -27%. In conclusion, chlorogenic acid, caffeine, and N-methyl pyridinium impair the expression of gastric acid secretion-related proteins in a time-dependent manner. Future work will be aimed at the elucidation of the cooperative interplay of individual components using recombinates of single coffee constituents.