title: Receptor agonism and antagonism of dietary bitter compounds.
abstract: Food contains complex blends of structurally diverse bitter compounds that trigger bitterness through activation of one or more of the ∼25 human TAS2 bitter taste receptors. It remains unsolved, however, whether the perceived bitterness of binary bitter-compound mixtures can be considered an additive function of all bitter-inducing chemicals in the mouth, suggesting that little mutual interaction takes place among bitter substances or if mixture suppression and synergism occurs. Here we report on two natural sesquiterpene lactones from edible plants, which stimulate distinct sets of hTAS2Rs in transfected cells. Both chemicals also robustly inhibit different but overlapping subsets of agonist-activated hTAS2Rs. These findings demonstrate that mixtures of bitter compounds, because they normally occur in human foodstuff, likely elicit bitter perception in a complex and not in a merely additive manner. An unexpected implication of this discovery is that, during evolution, the naturally occurring bitter taste receptor antagonists have shaped some of the pharmacological properties of the receptors, such as overlapping recognition profiles and breadth of tuning.
authors: German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany.
authors: Anne
authors: A
authors: Brockhoff
authors: Maik
authors: M
authors: Behrens
authors: Natacha
authors: N
authors: Roudnitzky
authors: Giovanni
authors: G
authors: Appendino
authors: Cristina
authors: C
authors: Avonto
authors: Wolfgang
authors: W
authors: Meyerhof
mesh_terms: D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D018684:Glycine Agents / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D009285:Naphthoquinones / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D012717:Sesquiterpenes / Q000494:pharmacology; D045789:Sesquiterpenes, Guaiane / Q000494:pharmacology; D013331:Strychnine / Q000494:pharmacology; D013649:Taste / Q000187:drug effects*; D013652:Taste Threshold / Q000187:drug effects* / Q000502:physiology; D014162:Transfection / Q000379:methods; D000098706:Taste Receptors, Type 2
chemical_list: D018684:Glycine Agents; D007783:Lactones; D009285:Naphthoquinones; D043562:Receptors, G-Protein-Coupled; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; C499475:absinthin; D000098706:Taste Receptors, Type 2; C024503:hydroxydihydrofusarubin; D013331:Strychnine; D002118:Calcium