title: Multi-parametric approach to identify coffee components that regulate mechanisms of gastric acid secretion.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  By applying a multi-parametric approach, N-MP was shown to effectively down-regulate mechanisms of gastric acid secretion in human parietal gastric cells.
authors.affiliation: German Research Center for Food Chemistry, Freising, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Rubach
authors.forename: Roman
authors.initials: R
authors.lastname: Lang
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Seebach
authors.forename: Mark M
authors.initials: MM
authors.lastname: Somoza
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofmann
authors.forename: Veronika
authors.initials: V
authors.lastname: Somoza
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D045744:Cell Line, Tumor; D002726:Chlorogenic Acid / Q000494:pharmacology; D003069:Coffee / Q000009:adverse effects* / Q000737:chemistry*; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation; D004357:Drug Synergism; D005744:Gastric Acid / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism; D011522:Protons; D011726:Pyridinium Compounds / Q000494:pharmacology; D011748:Pyrogallol / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D000470:Alkaloids; D002396:Catechols; D003069:Coffee; D011522:Protons; D011726:Pyridinium Compounds; D017481:Receptors, Somatostatin; D011748:Pyrogallol; D002726:Chlorogenic Acid; D002110:Caffeine; C009560:trigonelline; C014677:1-methylpyridinium; C093733:somatostatin receptor 2; D000242:Cyclic AMP; D017506:H(+)-K(+)-Exchanging ATPase; C034221:catechol