title: Bitter taste receptors for saccharin and acesulfame K.
abstract: Weight-conscious subjects and diabetics use the sulfonyl amide sweeteners saccharin and acesulfame K to reduce their calorie and sugar intake. However, the intrinsic bitter aftertaste, which is caused by unknown mechanisms, limits the use of these sweeteners. Here, we show by functional expression experiments in human embryonic kidney cells that saccharin and acesulfame K activate two members of the human TAS2R family (hTAS2R43 and hTAS2R44) at concentrations known to stimulate bitter taste. These receptors are expressed in tongue taste papillae. Moreover, the sweet inhibitor lactisole did not block the responses of cells transfected with TAS2R43 and TAS2R44, whereas it did block the response of cells expressing the sweet taste receptor heteromer hTAS1R2-hTAS1R3. The two receptors were also activated by nanomolar concentrations of aristolochic acid, a purely bitter-tasting compound. Thus, hTAS2R43 and hTAS2R44 function as cognate bitter taste receptors and do not contribute to the sweet taste of saccharin and acesulfame K. Consistent with the in vitro data, cross-adaptation studies in human subjects also support the existence of common receptors for both sulfonyl amide sweeteners.
authors.affiliation: German Institute of Human Nutrition Potsdam-Rehbruecke, Department of Molecular Genetics, 14558 Nuthetal, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Kuhn
authors.forename: Bernd
authors.initials: B
authors.lastname: Bufe
authors.forename: Marcel
authors.initials: M
authors.lastname: Winnig
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofmann
authors.forename: Oliver
authors.initials: O
authors.lastname: Frank
authors.forename: Maik
authors.initials: M
authors.lastname: Behrens
authors.forename: Tatjana
authors.initials: T
authors.lastname: Lewtschenko
authors.forename: Jay P
authors.initials: JP
authors.lastname: Slack
authors.forename: Cynthia D
authors.initials: CD
authors.lastname: Ward
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meyerhof
mesh_terms: D034341:Aristolochic Acids / Q000494:pharmacology; D001555:Benzene Derivatives / Q000494:pharmacology; D001592:Benzyl Alcohols / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000502:physiology; D005960:Glucosides; D006801:Humans; D007668:Kidney; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012439:Saccharin / Q000494:pharmacology*; D013549:Sweetening Agents / Q000494:pharmacology*; D013649:Taste / Q000502:physiology; D013843:Thiazines / Q000494:pharmacology*; D014059:Tongue / Q000502:physiology / Q000648:ultrastructure; D014162:Transfection; D000098706:Taste Receptors, Type 2
chemical_list: D034341:Aristolochic Acids; D001555:Benzene Derivatives; D001592:Benzyl Alcohols; D044385:GTP-Binding Protein alpha Subunits; D005960:Glucosides; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D013549:Sweetening Agents; D013843:Thiazines; C431926:taste receptors, type 1; D000098706:Taste Receptors, Type 2; C005696:salicin; C000228:aristolochic acid I; D012439:Saccharin; C006362:acetosulfame; C495512:lactisole