The Bitter-Tasting Amino Acids L-Arginine and L-Isoleucine Differentially Regulate Proton Secretion via T2R1 Signalling in Human Parietal Cells in Culture

This study aimed at identifying whether the bitter-tasting amino acids L arginine (L-ARG) and L isoleucine (L- ILE) differentially regulate mechanisms of gastric acid secretion (GAS) in human parietal cells (HGT-1 cells) via activation of bitter taste sensing receptors (T2Rs). In a first set of experiments, involvement of T2Rs in L-ARG and L-ILE-modulated proton secretion was demonstrated by co-treatment of HGT-1 cells with T2R antagonists. Subsequent whole genome screenings by means of cDNA arrays revealed T2R1 as a prominent target for both amino acids. Next, the functional role of T2R1 was verified by means of a T2R1 CRISPR-Cas9 knock out approach. Here, the effect of L-ARG on proton secretion decreased by 65.7 ± 21.9 % and the effect of L-ILE increased by 93.2 ± 24.1 % in HGT-1 T2R1 ko vs. HGT-1 wt cells (p<0.05). Overall, our results indicate differential effects of L-ARG and L-ILE on proton secretion in HGT-1 cells and our molecular docking studies predict distinct binding for these amino acids in t...