Bitter-Tasting Amino Acids <scp>l</scp>-Arginine and <scp>l</scp>-Isoleucine Differentially Regulate Proton Secretion via T2R1 Signaling in Human Parietal Cells in Culture

Stoeger, Verena; Holik, Ann‐Katrin; Hölz, Kathrin; Dingjan, Tamir; Hans, Joachim; Ley, Jakob P.; Krammer, Gerhard; Niv, Masha Y.; Somoza, Mark M.; Somoza, Veronika

doi:10.1021/acs.jafc.9b06285

Cited by 13 publications

(12 citation statements)

References 71 publications

(148 reference statements)

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“…3 In contrast, humans perceive most amino acids as a pleasant umami taste, 4 whereas some amino acids, such as arginine, isoleucine, tryptophan, and phenylalanine, are detected as bitter. 5,6 Amino acid taste receptors have been widely characterized in mammals and are known to consist of a heteromultimeric complex of T1R1 and T1R3 G protein-coupled receptors. 4 In flies, an ionotropic receptor 76b (IR76b) has been identified as a co-receptor for the perception of amino acids in both larvae and adults.…”

Section: Introductionmentioning

confidence: 99%

Molecular and neuronal mechanisms for amino acid taste perception in the Drosophila labellum

Aryal¹,

Dhakal²,

Shrestha³

et al. 2022

Current Biology

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Section: Introductionmentioning

confidence: 99%

Molecular and neuronal mechanisms for amino acid taste perception in the Drosophila labellum

Aryal¹,

Dhakal²,

Shrestha³

et al. 2022

Current Biology

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“…10 For L-arginine, one of the most bitter-tasting amino acids in our diet, our group also demonstrated a stimulation of cellular mechanisms regulating gastric acid secretion in cultured human parietal cells (HGT-1) via TAS2R1 signaling. 11,12 The underlying hypothesis of bitter-taste-sensing chemoreceptors being involved in gastric acid secretion was verified by preceding experiments, showing that the bitter-tasting caffeine stimulates (i) proton secretion via TAS2R signaling in TAS2R43 CRISPR-Cas9-edited human parietal HGT-1 cells in culture and (ii) promotes gastric acid secretion in healthy subjects, which was reduced by co-administration of the TAS2R antagonist homoeriodictyol. 13 Notably, administration of bitter-masking homoeriodictyol not only reduced the caffeine-evoked effect on gastric acid secretion but also increased gastric motility and emptying, decreased peripheral serotonin levels, and stimulated appetite.…”

Section: Introductionmentioning

confidence: 78%

Bitter Peptides YFYPEL, VAPFPEVF, and YQEPVLGPVRGPFPIIV, Released during Gastric Digestion of Casein, Stimulate Mechanisms of Gastric Acid Secretion via Bitter Taste Receptors TAS2R16 and TAS2R38

Richter

Sebald

Fischer

et al. 2022

J. Agric. Food Chem.

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Eating satiating, protein-rich foods is one of the key aspects of modern diet, although a bitter off-taste often limits the application of some proteins and protein hydrolysates, especially in processed foods. Previous studies of our group demonstrated that bitter-tasting food constituents, such as caffeine, stimulate mechanisms of gastric acid secretion as a signal of gastric satiation and a key process of gastric protein digestion via activation of bitter taste receptors (TAS2Rs). Here, we tried to elucidate whether dietary non-bitter-tasting casein is intra-gastrically degraded into bitter peptides that stimulate mechanisms of gastric acid secretion in physiologically achievable concentrations. An in vitro model of gastric digestion was verified by casein-fed pigs, and the peptides resulting from gastric digestion were identified by liquid chromatography–time-of-flight-mass spectrometry. The bitterness of five selected casein-derived peptides was validated by sensory analyses and by an in vitro screening approach based on human gastric parietal cells (HGT-1). For three of these peptides (YFYPEL, VAPFPEVF, and YQEPVLGPVRGPFPIIV), an upregulation of gene expression of TAS2R16 and TAS2R38 was observed. The functional involvement of these TAS2Rs was verified by siRNA knock-down (kd) experiments in HGT-1 cells. This resulted in a reduction of the mean proton secretion promoted by the peptides by up to 86.3 ± 9.9% for TAS2R16kd (p < 0.0001) cells and by up to 62.8 ± 7.0% for TAS2R38kd (p < 0.0001) cells compared with mock-transfected cells.

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“…After a 10 min incubation time with 0.1 µM serotonin, HGT-1 cells showed a reduced proton secretion in comparison to the untreated control analyzed by means of intracellular proton index (IPX) (0.21 ± 0.03 vs. control −0.00 ± 0.02) ( Figure 6 A). Tested serotonin and L-Arg concentrations are based on physiologically relevant concentrations [ 41 , 42 , 43 ]. Incubation with 10 µM of the 5-HT3 receptor antagonist granisetron reduced the L-Arg-induced proton secretion from IPX −3.48 ± 0.13 to −3.00 ± 0.53 ( p < 0.05, Figure 6 B), while incubation with SERT inhibitor fluoxetine showed no impact ( Figure S6 ).…”

Section: Resultsmentioning

confidence: 99%

Gastric Serotonin Biosynthesis and Its Functional Role in L-Arginine-Induced Gastric Proton Secretion

Holik

Schweiger

Stoeger

et al. 2021

IJMS

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Among mammals, serotonin is predominantly found in the gastrointestinal tract, where it has been shown to participate in pathway-regulating satiation. For the stomach, vascular serotonin release induced by gastric distension is thought to chiefly contribute to satiation after food intake. However, little information is available on the capability of gastric cells to synthesize, release and respond to serotonin by functional changes of mechanisms regulating gastric acid secretion. We investigated whether human gastric cells are capable of serotonin synthesis and release. First, HGT-1 cells, derived from a human adenocarcinoma of the stomach, and human stomach specimens were immunostained positive for serotonin. In HGT-1 cells, incubation with the tryptophan hydroxylase inhibitor p-chlorophenylalanine reduced the mean serotonin-induced fluorescence signal intensity by 27%. Serotonin release of 147 ± 18%, compared to control HGT-1 cells (set to 100%) was demonstrated after treatment with 30 mM of the satiating amino acid L-Arg. Granisetron, a 5-HT3 receptor antagonist, reduced this L-Arg-induced serotonin release, as well as L-Arg-induced proton secretion. Similarly to the in vitro experiment, human antrum samples released serotonin upon incubation with 10 mM L-Arg. Overall, our data suggest that human parietal cells in culture, as well as from the gastric antrum, synthesize serotonin and release it after treatment with L-Arg via an HTR3-related mechanism. Moreover, we suggest not only gastric distension but also gastric acid secretion to result in peripheral serotonin release.

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Bitter-Tasting Amino Acids l-Arginine and l-Isoleucine Differentially Regulate Proton Secretion via T2R1 Signaling in Human Parietal Cells in Culture

Cited by 13 publications

References 71 publications

Molecular and neuronal mechanisms for amino acid taste perception in the Drosophila labellum

Molecular and neuronal mechanisms for amino acid taste perception in the Drosophila labellum

Bitter Peptides YFYPEL, VAPFPEVF, and YQEPVLGPVRGPFPIIV, Released during Gastric Digestion of Casein, Stimulate Mechanisms of Gastric Acid Secretion via Bitter Taste Receptors TAS2R16 and TAS2R38

Gastric Serotonin Biosynthesis and Its Functional Role in L-Arginine-Induced Gastric Proton Secretion

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