6-methoxyflavanones as bitter taste receptor blockers for hTAS2R39

• Published in: PloS one 2014-04, Vol.9 (4), p.e94451-e94451
• Main Authors: Roland, Wibke S U, Gouka, Robin J, Gruppen, Harry, Driesse, Marianne, van Buren, Leo, Smit, Gerrit, Vincken, Jean-Paul
• Format: Article
• Language: English
• Subjects: Activation; Amino acids; Analysis; Biological Assay; Biology and Life Sciences; Bitter taste; Caffeine; Calcium - metabolism; Calcium Signaling; Catechin - analogs & derivatives; Catechin - antagonists & inhibitors; Catechin - chemistry; Catechin - pharmacology; Chemistry; Cloning; Diet; Electrocardiogram; Electrocardiography; Epicatechin; Flavanones - chemistry; Flavanones - pharmacology; Flavonoids; Food; Gene Expression; Green tea; HEK293 Cells; Humans; Isoflavones; Laboratories; Medicine and Health Sciences; Peptides; Physical Sciences; Physiological aspects; Protein Binding; Proteins; Quaternary Ammonium Compounds - chemistry; Quaternary Ammonium Compounds - pharmacology; Receptors, Cell Surface - agonists; Receptors, Cell Surface - antagonists & inhibitors; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - antagonists & inhibitors; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Sensory perception; Structure-Activity Relationship; Taste; Taste - physiology; Tea; Tea - chemistry; Tongue; Transgenes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0094451

Many (dietary) bitter compounds, e.g. flavonoids, activate bitter receptor hTAS2R39 in cell-based assays. Several flavonoids, amongst which some flavanones, are known not to activate this receptor. As certain flavanones are known to mask bitter taste sensorially, flavanones might act as bitter receptor antagonists. Fourteen flavanones were investigated for their potential to reduce activation of hTAS2R39 by epicatechin gallate (ECG), one of the main bitter compounds occurring in green tea. Three flavanones showed inhibitory behavior towards the activation of hTAS2R39 by ECG: 4'-fluoro-6-methoxyflavanone, 6,3'-dimethoxyflavanone, and 6-methoxyflavanone (in order of decreasing potency). The 6-methoxyflavanones also inhibited activation of hTAS2R14 (another bitter receptor activated by ECG), though to a lesser extent. Dose-response curves of ECG at various concentrations of the full antagonist 4'-fluoro-6-methoxyflavanone and wash-out experiments indicated reversible insurmountable antagonism. The same effect was observed for the structurally different agonist denatonium benzoate.