期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 68, 期 11, 页码 3434-3444出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.9b06285
关键词
amino acids; bitter taste; gastric acid secretion; HGT-1 cells; T2R
资金
- Austrian Federal Ministry of Economy, the Family and Youth
- Austrian National Foundation for Research, Technology, and Development
- EMBO (European Molecular Biology Organisation)
- COST action MuTaLig (Multi-target paradigm for innovative ligand identification in the drug discovery process)
- Austrian Science Fund (FWF) [P30596]
- German Research Foundation [Gm 13/12]
- Symrise AG
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 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 versus HGT-1 wt cells (p < 0.05). Overall, our results indicate differential effects of LARG and L-ILE on proton secretion in HGT-1 cells and our molecular docking studies predict distinct binding for these amino acids in the binding site of T2R1. Further studies will elucidate whether the mechanism of differential effects involves structure-specific ligand-biased signaling of T2R1 or additional cellular targets.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据