Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells

Kathrin Ingrid Liszt, Jakob Peter Ley, Barbara Lieder, Maik Behrens, Verena Stöger, Angelika Reiner, Christina Maria Hochkogler, Elke Köck, Alessandro Marchiori, Joachim Hans, Sabine Widder, Gerhard Krammer, Gareth John Sanger, Mark Manuel Somoza, Wolfgang Meyerhof, Veronika Somoza

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Caffeine, generally known as a stimulant of gastric acid secretion (GAS), is a bitter-tasting compound that activates several taste type 2 bitter receptors (TAS2Rs). TAS2Rs are expressed in the mouth and in several extraoral sites, e.g., in the gastrointestinal tract, in which their functional role still needs to be clarified. We hypothesized that caffeine evokes effects on GAS by activation of oral and gastric TAS2Rs and demonstrate that caffeine, when administered encapsulated, stimulates GAS, whereas oral administration of a caffeine solution delays GAS in healthy human subjects. Correlation analysis of data obtained from ingestion of the caffeine solution revealed an association between the magnitude of the GAS response and the perceived bitterness, suggesting a functional role of oral TAS2Rs in GAS. Expression of TAS2Rs, including cognate TAS2Rs for caffeine, was shown in human gastric epithelial cells of the corpus/fundus and in HGT-1 cells, a model for the study of GAS. In HGT-1 cells, various bitter compounds as well as caffeine stimulated proton secretion, whereby the caffeine-evoked effect was (i) shown to depend on one of its cognate receptor, TAS2R43, and adenylyl cyclase; and (ii) reduced by homoeriodictyol (HED), a known inhibitor of caffeine’s bitter taste. This inhibitory effect of HED on caffeine-induced GAS was verified in healthy human subjects. These findings (i) demonstrate that bitter taste receptors in the stomach and the oral cavity are involved in the regulation of GAS and (ii) suggest that bitter tastants and bitter-masking compounds could be potentially useful therapeutics to regulate gastric pH.

Original languageEnglish
Pages (from-to)E6260-E6269
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number30
DOIs
StatePublished - 25 Jul 2017
Externally publishedYes

Keywords

  • Bitter taste receptors
  • Caffeine
  • Gastric acid secretion
  • Homoeriodictyol
  • TAS2Rs

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