title: Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium.
abstract: Sesquiterpene lactones are a major class of natural bitter compounds occurring in vegetables and culinary herbs as well as in aromatic and medicinal plants, where they often represent the main gustatory and pharmacologically active component. Investigations on sesquiterpene lactones have mainly focused on their bioactive potential rather than on their sensory properties. In the present study, we report about the stimulation of heterologously expressed human bitter taste receptors, hTAS2Rs, by the bitter sesquiterpene lactone herbolide D. A specific response to herbolide D was observed i.a. for hTAS2R46, a so far orphan bitter taste receptor without any known ligand. By further investigation of its agonist pattern, we characterized hTAS2R46 as a bitter receptor broadly tuned to sesquiterpene lactones and to clerodane and labdane diterpenoids as well as to the unrelated bitter substances strychnine and denatonium.
authors.affiliation: Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Brockhoff
authors.forename: Maik
authors.initials: M
authors.lastname: Behrens
authors.forename: Alberto
authors.initials: A
authors.lastname: Massarotti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Appendino
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meyerhof
mesh_terms: D004224:Diterpenes / Q000494:pharmacology*; D045785:Diterpenes, Clerodane / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000235:genetics; D012717:Sesquiterpenes / Q000494:pharmacology*; D013331:Strychnine / Q000494:pharmacology*; D000098706:Taste Receptors, Type 2
chemical_list: D004224:Diterpenes; D045785:Diterpenes, Clerodane; D007783:Lactones; D000644:Quaternary Ammonium Compounds; D043562:Receptors, G-Protein-Coupled; D012717:Sesquiterpenes; D013331:Strychnine; D000098706:Taste Receptors, Type 2; C433017:labdane; C043414:denatonium