6-methoxyflavanones as bitter taste receptor blockers for hTAS2R39.
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.
Laboratory of Food Chemistry, Wageningen University, Wageningen, The Netherlands.
Wibke S U
WS
Roland
Unilever R&D, Vlaardingen, The Netherlands.
Robin J
RJ
Gouka
Laboratory of Food Chemistry, Wageningen University, Wageningen, The Netherlands.
Harry
H
Gruppen
Laboratory of Food Chemistry, Wageningen University, Wageningen, The Netherlands.
Marianne
M
Driesse
Unilever R&D, Vlaardingen, The Netherlands.
Leo
L
van Buren
Laboratory of Food Chemistry, Wageningen University, Wageningen, The Netherlands.
Gerrit
G
Smit
Laboratory of Food Chemistry, Wageningen University, Wageningen, The Netherlands.
Jean-Paul
JP
Vincken
D001681:Biological Assay; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002392:Catechin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D011485:Protein Binding; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013649:Taste / Q000502:physiology; D013662:Tea / Q000737:chemistry; D019076:Transgenes; D000098706:Taste Receptors, Type 2
D002118:Calcium; D002392:Catechin; D044950:Flavanones; D000644:Quaternary Ammonium Compounds; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013662:Tea; D000098706:Taste Receptors, Type 2; C557300:TAS2R39 protein, human; C062669:epicatechin gallate; C043414:denatonium