TY - JOUR
T1 - Multi-parametric approach to identify coffee components that regulate mechanisms of gastric acid secretion
AU - Rubach, Malte
AU - Lang, Roman
AU - Seebach, Elisabeth
AU - Somoza, Mark M.
AU - Hofmann, Thomas
AU - Somoza, Veronika
PY - 2012/2
Y1 - 2012/2
N2 - Scope: Chlorogenic acid (CA), caffeine (CAFF), pyrogallol (PYR), catechol (CAT), βN-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.
AB - Scope: Chlorogenic acid (CA), caffeine (CAFF), pyrogallol (PYR), catechol (CAT), βN-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.
KW - Coffee
KW - Gastric acid secretion
KW - H ,K -ATPase
KW - Neural network
KW - SSTR2-receptor
UR - https://www.scopus.com/pages/publications/84856908740
U2 - 10.1002/mnfr.201100453
DO - 10.1002/mnfr.201100453
M3 - Article
C2 - 22147653
AN - SCOPUS:84856908740
SN - 1613-4125
VL - 56
SP - 325
EP - 335
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - 2
ER -