6-methoxyflavanones as bitter taste receptor blockers for hTAS2R39

PLoS One. 2014 Apr 10;9(4):e94451. doi: 10.1371/journal.pone.0094451. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Assay
  • Calcium / metabolism
  • Calcium Signaling
  • Catechin / analogs & derivatives*
  • Catechin / antagonists & inhibitors
  • Catechin / chemistry
  • Catechin / pharmacology
  • Flavanones / chemistry
  • Flavanones / pharmacology*
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Protein Binding
  • 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*
  • Structure-Activity Relationship
  • Taste / physiology
  • Tea / chemistry
  • Transgenes

Substances

  • Flavanones
  • Quaternary Ammonium Compounds
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • TAS2R39 protein, human
  • Tea
  • taste receptors, type 2
  • denatonium benzoate
  • Catechin
  • epicatechin gallate
  • Calcium

Grant support

This work was financially supported by the Food & Nutrition Delta of the Ministry of Economic Affairs, the Netherlands (FND 08019, http://www.agentschapnl.nl/subsidies-regelingen/innovatieprogramma-food—nutrition). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.