T2Rs function as bitter taste receptors

Cell. 2000 Mar 17;100(6):703-11. doi: 10.1016/s0092-8674(00)80706-0.


Bitter taste perception provides animals with critical protection against ingestion of poisonous compounds. In the accompanying paper, we report the characterization of a large family of putative mammalian taste receptors (T2Rs). Here we use a heterologous expression system to show that specific T2Rs function as bitter taste receptors. A mouse T2R (mT2R-5) responds to the bitter tastant cycloheximide, and a human and a mouse receptor (hT2R-4 and mT2R-8) responded to denatonium and 6-n-propyl-2-thiouracil. Mice strains deficient in their ability to detect cycloheximide have amino acid substitutions in the mT2R-5 gene; these changes render the receptor significantly less responsive to cycloheximide. We also expressed mT2R-5 in insect cells and demonstrate specific tastant-dependent activation of gustducin, a G protein implicated in bitter signaling. Since a single taste receptor cell expresses a large repertoire of T2Rs, these findings provide a plausible explanation for the uniform bitter taste that is evoked by many structurally unrelated toxic compounds.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Afferent Pathways / chemistry
  • Afferent Pathways / physiology
  • Amino Acid Sequence
  • Animals
  • Calcium / analysis
  • Cell Line
  • Chemoreceptor Cells / chemistry*
  • Chemoreceptor Cells / physiology
  • Cycloheximide
  • Gene Expression / physiology
  • Humans
  • Kidney / cytology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Molecular Sequence Data
  • Protein Synthesis Inhibitors
  • Quaternary Ammonium Compounds
  • Receptors, Cell Surface / analysis
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism*
  • Receptors, G-Protein-Coupled*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / physiology
  • Taste / physiology*
  • Taste Buds / chemistry*
  • Taste Buds / physiology
  • Transducin / metabolism
  • Transfection


  • Protein Synthesis Inhibitors
  • Quaternary Ammonium Compounds
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Recombinant Fusion Proteins
  • taste receptors, type 2
  • gustducin
  • denatonium benzoate
  • Cycloheximide
  • Transducin
  • Calcium