The molecular receptive ranges of human TAS2R bitter taste receptors.
Humans perceive thousands of compounds as bitter. In sharp contrast, only approximately 25 taste 2 receptors (TAS2R) bitter taste receptors have been identified, raising the question as to how the vast array of bitter compounds can be detected by such a limited number of sensors. To address this issue, we have challenged 25 human taste 2 receptors (hTAS2Rs) with 104 natural or synthetic bitter chemicals in a heterologous expression system. Thirteen cognate bitter compounds for 5 orphan receptors and 64 new compounds for previously identified receptors were discovered. Whereas some receptors recognized only few agonists, others displayed moderate or extreme tuning broadness. Thus, 3 hTAS2Rs together were able to detect approximately 50% of the substances used. Conversely, though 63 bitter substances activated only 1-3 receptors, 19 compounds stimulated up to 15 hTAS2Rs. Our data suggest that the detection of the numerous bitter chemicals is related to the molecular receptive ranges of hTAS2Rs.
Meyerhof
Wolfgang
W
Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany. meyerhof@dife.de
Batram
Claudia
C
Kuhn
Christina
C
Brockhoff
Anne
A
Chudoba
Elke
E
Bufe
Bernd
B
Appendino
Giovanni
G
Behrens
Maik
M
D000814:Aniline Compounds / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*; D013649:Taste / Q000187:drug effects / Q000502:physiology*; D013652:Taste Threshold; D014966:Xanthenes / Q000494:pharmacology; D000098706:Taste Receptors, Type 2
D000814:Aniline Compounds; C409648:Fluo 4; D005456:Fluorescent Dyes; D043562:Receptors, G-Protein-Coupled; D014966:Xanthenes; D000098706:Taste Receptors, Type 2