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

Mol Nutr Food Res. 2012 Feb;56(2):325-35. doi: 10.1002/mnfr.201100453. Epub 2011 Dec 7.


Scope: Chlorogenic acid (CA), caffeine (CAFF), pyrogallol (PYR), catechol (CAT), (β)N-alkanoyl-hydroxytryptamides (C5HT) and N-methylpyridinium (N-MP) were evaluated for their influence on mechanisms 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 down-regulate mechanisms of gastric acid secretion in human parietal gastric cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 2 / genetics
  • Activating Transcription Factor 2 / metabolism
  • Alkaloids / pharmacology
  • Caffeine / pharmacology
  • Catechols / pharmacology
  • Cell Line, Tumor
  • Chlorogenic Acid / pharmacology
  • Coffee / adverse effects*
  • Coffee / chemistry*
  • Cyclic AMP / metabolism
  • Down-Regulation
  • Drug Synergism
  • Gastric Acid / metabolism*
  • Gene Expression Regulation / drug effects
  • H(+)-K(+)-Exchanging ATPase / genetics
  • H(+)-K(+)-Exchanging ATPase / metabolism
  • Humans
  • Parietal Cells, Gastric / drug effects*
  • Parietal Cells, Gastric / metabolism
  • Protons
  • Pyridinium Compounds / pharmacology
  • Pyrogallol / pharmacology
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / metabolism


  • ATF2 protein, human
  • Activating Transcription Factor 2
  • Alkaloids
  • Catechols
  • Coffee
  • Protons
  • Pyridinium Compounds
  • Receptors, Somatostatin
  • Pyrogallol
  • Chlorogenic Acid
  • Caffeine
  • trigonelline
  • 1-methylpyridinium
  • somatostatin receptor 2
  • Cyclic AMP
  • H(+)-K(+)-Exchanging ATPase
  • catechol