Mammalian bitter taste perception.

Bitter taste in mammals is achieved by a family of approximately 30 bitter taste receptor genes. The main function of bitter taste is to protect the organism against the ingestion of, frequently bitter, toxic food metabolites. The field of taste research has advanced rapidly during the last several years. This is especially true for the G-protein-coupled-receptor-mediated taste qualities, sweet, umami, and bitter. This review summarizes current knowledge of bitter taste receptor gene expression, signal transduction, the structure-activity relationship of bitter taste receptor proteins, as well as their variability leading to a high degree of individualization of this taste quality in mammals.

[1]  Hong Xu,et al.  Receptors for bitter, sweet and umami taste couple to inhibitory G protein signaling pathways. , 2004, European journal of pharmacology.

[2]  T. Finger,et al.  Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[3]  A. Sclafani,et al.  Rats show only a weak preference for the artificial sweetener aspartame , 1986, Physiology & Behavior.

[4]  N. Ryba,et al.  T2Rs Function as Bitter Taste Receptors , 2000, Cell.

[5]  S. Arai,et al.  Taste Buds Have a Cyclic Nucleotide-activated Channel, CNGgust* , 1997, The Journal of Biological Chemistry.

[6]  Mark Leppert,et al.  Positional Cloning of the Human Quantitative Trait Locus Underlying Taste Sensitivity to Phenylthiocarbamide , 2003, Science.

[7]  A. Robichon,et al.  Coupling of bitter receptor to phosphodiesterase through transducin in taste receptor cells , 1995, Nature.

[8]  M. Bamshad,et al.  Independent evolution of bitter-taste sensitivity in humans and chimpanzees , 2006, Nature.

[9]  E. Rozengurt,et al.  Enteroendocrine cells: a site of ‘taste’ in gastrointestinal chemosensing , 2008, Current opinion in endocrinology, diabetes, and obesity.

[10]  J. Boughter,et al.  Behavioral genetics and taste , 2007, BMC Neuroscience.

[11]  R. Margolskee,et al.  Molecular cloning of G proteins and phosphodiesterases from rat taste cells , 1994, Physiology & Behavior.

[12]  A. Sbarbati,et al.  A new fate for old cells: brush cells and related elements , 2005, Journal of anatomy.

[13]  David V. Smith,et al.  Differential covariation in taste responsiveness to bitter stimuli in rats. , 2005, Chemical senses.

[14]  K. Gannon,et al.  Transduction of bitter and sweet taste by gustducin , 1996, Nature.

[15]  J. Boughter,et al.  Inbred mouse strains C57BL/6J and DBA/2J vary in sensitivity to a subset of bitter stimuli , 2005, BMC Genetics.

[16]  L. Snyder,et al.  The Cysteine-rich Region of T1R3 Determines Responses to Intensely Sweet Proteins* , 2004, Journal of Biological Chemistry.

[17]  L. Jorde,et al.  Worldwide haplotype diversity and coding sequence variation at human bitter taste receptor loci , 2005, Human mutation.

[18]  P. Shi,et al.  Extraordinary diversity of chemosensory receptor gene repertoires among vertebrates. , 2009, Results and problems in cell differentiation.

[19]  A. Sbarbati,et al.  Secretory cells of the airway express molecules of the chemoreceptive cascade , 2007, Cell and Tissue Research.

[20]  Dietmar Krautwurst,et al.  The human TAS2R16 receptor mediates bitter taste in response to β-glucopyranosides , 2002, Nature Genetics.

[21]  L. M. Beidler,et al.  RENEWAL OF CELLS WITHIN TASTE BUDS , 1965, The Journal of cell biology.

[22]  R. Margolskee,et al.  α Gustducin: A Taste Cell Specific G Protein Subunit Closely Related to the α Transducins , 1992 .

[23]  Michael J Bamshad,et al.  Natural selection and molecular evolution in PTC, a bitter-taste receptor gene. , 2004, American journal of human genetics.

[24]  Xiaodong Li,et al.  Human receptors for sweet and umami taste , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Monica C. Chen,et al.  Genomic organization, expression, and function of bitter taste receptors (T2R) in mouse and rat. , 2005, Physiological genomics.

[26]  Liquan Huang,et al.  Gγ13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium , 1999, Nature Neuroscience.

[27]  T. R. Scott,et al.  Taste as a factor in the management of nutrition. , 2000, Nutrition.

[28]  H. Breer,et al.  G protein betagamma complexes in circumvallate taste cells involved in bitter transduction. , 2000, Chemical senses.

[29]  Yuji Imaizumi,et al.  Functional Interaction between T2R Taste Receptors and G-Protein α Subunits Expressed in Taste Receptor Cells , 2003, The Journal of Neuroscience.

[30]  S. Kinnamon,et al.  Making sense with TRP channels: store-operated calcium entry and the ion channel Trpm5 in taste receptor cells. , 2003, Cell calcium.

[31]  H. Kalmus,et al.  Taste thresholds of further eighteen compounds and their correlation with P.T.C thresholds. , 1951, Annals of eugenics.

[32]  S. Kinnamon,et al.  Bitter Taste Transduction of Denatonium in the MudpuppyNecturus maculosus , 1997, The Journal of Neuroscience.

[33]  Edmund T. Rolls,et al.  Central taste anatomy and neurophysiology. , 2003 .

[34]  C. Zancanaro,et al.  α‐Gustducin expression in the vomeronasal organ of the mouse , 1999, The European journal of neuroscience.

[35]  Hong Wang,et al.  Pseudogenization of a Sweet-Receptor Gene Accounts for Cats' Indifference toward Sugar , 2005, PLoS genetics.

[36]  Jianzhi Zhang,et al.  Contrasting modes of evolution between vertebrate sweet/umami receptor genes and bitter receptor genes. , 2006, Molecular biology and evolution.

[37]  I. J. Miller,et al.  Variations in human taste bud density and taste intensity perception , 1990, Physiology & Behavior.

[38]  Linda B. Buck,et al.  A family of candidate taste receptors in human and mouse , 2000, Nature.

[39]  A. Pronin,et al.  Identification of ligands for two human bitter T2R receptors. , 2004, Chemical senses.

[40]  A. L. Fox The Relationship between Chemical Constitution and Taste. , 1932, Proceedings of the National Academy of Sciences of the United States of America.

[41]  Andrew I. Spielman,et al.  Bitter taste transduced by PLC-β2-dependent rise in IP3 and α-gustducin-dependent fall in cyclic nucleotides , 2001 .

[42]  R. Penner,et al.  TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in [Ca2+]i , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Xiaodong Li,et al.  Specific Alleles of Bitter Receptor Genes Influence Human Sensitivity to the Bitterness of Aloin and Saccharin , 2007, Current Biology.

[44]  H. Breer,et al.  G Protein βγ Complexes in Circumvallate Taste Cells Involved in Bitter Transduction , 2000 .

[45]  E. Liman,et al.  Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5 , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[46]  Xiaodong Li,et al.  Different functional roles of T1R subunits in the heteromeric taste receptors. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[47]  N. Ryba,et al.  Putative Mammalian Taste Receptors A Class of Taste-Specific GPCRs with Distinct Topographic Selectivity , 1999, Cell.

[48]  G. Beauchamp,et al.  Individual differences in sensitivity to bitter-tasting substances , 1993 .

[49]  V. Collings Human taste response as a function of locus of stimulation on the tongue and soft palate , 1974 .

[50]  Y. Zotterman,et al.  Electrophysiological study of the gustatory effects of the sweet proteins monellin and thaumatin in monkey, guinea pig and rat. , 1973, Acta physiologica Scandinavica.

[51]  J. Slack,et al.  The Molecular Basis of Individual Differences in Phenylthiocarbamide and Propylthiouracil Bitterness Perception , 2005, Current Biology.

[52]  Jianzhi Zhang,et al.  Adaptive diversification of bitter taste receptor genes in Mammalian evolution. , 2003, Molecular biology and evolution.

[53]  T. Gudermann,et al.  TRPM5 Is a Voltage-Modulated and Ca2+-Activated Monovalent Selective Cation Channel , 2003, Current Biology.

[54]  S. H. Young,et al.  Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[55]  M. Behrens,et al.  The human taste receptor hTAS2R14 responds to a variety of different bitter compounds. , 2004, Biochemical and biophysical research communications.

[56]  P. Breslin,et al.  A psychophysical investigation of binary bitter-compound interactions. , 2003, Chemical senses.

[57]  H. Breer,et al.  Identification of a phospholipase C beta subtype in rat taste cells. , 1998, European journal of cell biology.

[58]  Liquan Huang,et al.  A transient receptor potential channel expressed in taste receptor cells , 2002, Nature Neuroscience.

[59]  A. Sbarbati,et al.  α-Gustducin immunoreactivity in the airways , 2005, Cell and Tissue Research.

[60]  N. Ryba,et al.  Coding of Sweet, Bitter, and Umami Tastes Different Receptor Cells Sharing Similar Signaling Pathways , 2003, Cell.

[61]  A. Sbarbati,et al.  Laryngeal chemosensory clusters. , 2004, Chemical senses.

[62]  Liquan Huang,et al.  Bitter peptides activate hTAS2Rs, the human bitter receptors. , 2008, Biochemical and biophysical research communications.

[63]  S. Travers,et al.  Single neurons in the nucleus of the solitary tract respond selectively to bitter taste stimuli. , 2006, Journal of neurophysiology.

[64]  Bernd Nilius,et al.  Heat activation of TRPM5 underlies thermal sensitivity of sweet taste , 2005, Nature.

[65]  Jayaram Chandrashekar,et al.  The cells and logic for mammalian sour taste detection , 2006, Nature.

[66]  James F Battey,et al.  Functional characterization of human bitter taste receptors. , 2007, The Biochemical journal.

[67]  S. Roper,et al.  Taste Receptor Cells That Discriminate Between Bitter Stimuli , 2001, Science.

[68]  Alberto Massarotti,et al.  Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium. , 2007, Journal of agricultural and food chemistry.

[69]  R. Margolskee,et al.  Trpm5 null mice respond to bitter, sweet, and umami compounds. , 2006, Chemical senses.

[70]  A. Farbman RENEWAL OF TASTE BUD CELLS IN RAT CIRCUMVALLATE PAPILLAE , 1980, Cell and tissue kinetics.

[71]  L. Bartoshuk,et al.  Comparing sensory experiences across individuals: recent psychophysical advances illuminate genetic variation in taste perception. , 2000, Chemical senses.

[72]  N. Ryba,et al.  Mammalian Sweet Taste Receptors , 2001, Cell.

[73]  Pardis C Sabeti,et al.  Positive Selection on a High-Sensitivity Allele of the Human Bitter-Taste Receptor TAS2R16 , 2005, Current Biology.

[74]  N. Ryba,et al.  The Receptors for Mammalian Sweet and Umami Taste , 2003, Cell.

[75]  A. Sbarbati,et al.  alpha-Gustducin immunoreactivity in the airways. , 2005, Cell and tissue research.

[76]  S. Roper,et al.  PLCbeta2-independent behavioral avoidance of prototypical bitter-tasting ligands. , 2005, Chemical senses.

[77]  Thomas Hofmann,et al.  Bitter Taste Receptors for Saccharin and Acesulfame K , 2004, The Journal of Neuroscience.

[78]  Gustatory Neural Coding , 2003 .

[79]  P. Breslin,et al.  Covariation in individuals’ sensitivities to bitter compounds: Evidence supporting multiple receptor/transduction mechanisms , 2001, Perception & psychophysics.

[80]  Jayaram Chandrashekar,et al.  A Novel Family of Mammalian Taste Receptors , 2000, Cell.

[81]  R. Erickson,et al.  Neural responses to bitter compounds in rats , 1997, Brain Research.

[82]  M. Behrens,et al.  Signaling in chemosensory systems , 2006, Cellular and Molecular Life Sciences CMLS.

[83]  L. T. Do,et al.  Neurophysiology of geniculate ganglion (facial nerve) taste systems: species comparisons , 1985 .

[84]  S. Kinnamon,et al.  Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction , 2001, BMC Neuroscience.

[85]  S. Kopka,et al.  Rats Fail to Discriminate Quinine from Denatonium: Implications for the Neural Coding of Bitter-Tasting Compounds , 2002, The Journal of Neuroscience.

[86]  David V. Smith,et al.  Neuronal cell types and taste quality coding , 2000, Physiology & Behavior.

[87]  J. Trowsdale,et al.  Comparative Genomics of Natural Killer Cell Receptor Gene Clusters , 2005, PLoS genetics.

[88]  R. Margolskee,et al.  Directing Gene Expression to Gustducin-Positive Taste Receptor Cells , 1999, The Journal of Neuroscience.

[89]  M. Behrens,et al.  Gustatory Expression Pattern of the Human TAS2R Bitter Receptor Gene Family Reveals a Heterogenous Population of Bitter Responsive Taste Receptor Cells , 2007, The Journal of Neuroscience.