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

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 caffeineevoked 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 bittermasking compounds could be potentially useful therapeutics to regulate gastric pH.gastric acid secretion | caffeine | homoeriodictyol | bitter taste receptors | TAS2Rs

Bitter substances from plants used in traditional Chinese medicine exert biased activation of human bitter taste receptors

“…Compounds reported previously to activate TAS2Rs are indicated by #, compounds for which the activation of TAS2Rs could not be confirmed are labeled by §. Examples for TAS2Rs that have been associated with non‐gustatory functions in brain, gastrointestinal tissues, respiratory epithelia, thyroid gland, leukocytes, and vascular smooth muscle cells are printed in bold.…”

Obesity alters adrenergic and chemosensory signaling pathways that regulate ghrelin secretion in the human gut

“…The colocalization of TAS2R10 with the ghrelin cell and the strong stimulatory effect of the TAS2R10 agonist, erythromycin A, on ghrelin secretion point toward an important role of TAS2R10. Previous studies have shown that TAS2R10 was also expressed in human gastric parietal cells (55).…”

Distinct Cell Types With the Bitter Receptor Tas2r126 in Different Compartments of the Stomach

“…In view of possible implications it will be of great interest to further explore whether individual combinations of receptor types may be expressed in distinct cell types or in cells at certain positions. This would allow defined responses to various bitter compounds and may explain diverse effects of bitter compounds on stomach functions, such as gastric emptying (Glendinning et al, 2008), antral contractility, stimulation of ghrelin release (Janssen et al, 2011(Janssen et al, , 2012Wang et al, 2019) and induction of gastric acid secretion (Liszt et al, 2017(Liszt et al, , 2018.…”

“…However, very little is known about the expression of bitter receptors in the stomach. The current information is mainly based on PCR analyses (Wu et al, 2002(Wu et al, , 2005Vegezzi et al, 2014;Prandi et al, 2018); only recently immunohistochemical evidence was presented for the presence of TAS2R10 receptor protein in parietal and chief cells of human stomach (Liszt et al, 2017).…”