Forskning

December 14, 2011

Multi-parametric approach to identify coffee components that regulate mechanisms of gastric acid secretion

M Rubach et al, Multi-parametric approach to identify coffee components that regulate mechanisms of gastric acid secretion, Mol Nutr Food Res, 2011, published online ahead of print.

Scope: Chlorogenic acid (CA), caffeine (CAFF), pyrogallol (PYR), catechol (CAT), βN-alkanoylhydroxytryptamides(C5HT) and N-methylpyridinium (N-MP) were evaluated for their influence onmechanisms of gastric acid secretion as single compounds and in biomimetic mixtures. Methods and results: Compounds were tested in coffee representative concentrations. Human gastric cancer cells (HGT-1) were used to study the proton secretory activity by Ussing chamber experiments and FACS analysis. For activation of EGFr, Akt1, ERK1/2, ATF-2 and cAMP levels, we performed pathway screening assays. Time-dependent expression of related genes were determined by real-time PCR. Part of the data was used for neural network modeling to identify the most relevant compounds. N-MP increased the expression of the anti-secretory somatostatin receptor by 114%, whereas C5HT decreased its expression by 52%. N-MP down-regulated the pro-secretory CHRM3 receptor by 36% and the H+,K+-ATPase by 36%. CAFF stimulated the secretory activity in the functional assays, whereas N-MP and CA decreased proton secretion. After applying a pathway analysis, we were able to discriminate between CAFF, CA, CAT, C5HT, PYR and histamine-activating EGFr signaling and N-MP-associated ERK1/2 signaling. Conclusion: By applying a multi-parametric approach, N-MP was shown to effectively downregulate mechanisms of gastric acid secretion in human parietal gastric cells.