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Elucidation of mammalian bitter taste

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Book cover Reviews of Physiology, Biochemistry and Pharmacology

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 154))

Abstract

A family of approximately 30 TAS2R bitter taste receptors has been identified in mammals. Their genes evolved through adaptive diversification and are linked to chromosomal loci known to influence bitter taste in mice and humans. The agonists for various TAS2Rs have been identified and all of them were established as bitter tastants. TAS2Rs are broadly tuned to detect multiple bitter substances, explaining, in part, how mammals can recognize numerous bitter compounds with a limited set of receptors. The TAS2Rs are expressed in a subset of taste receptor cells, which are distinct from those mediating responses to other taste qualities. However, cells devoted to the detection of sweet, umami, and bitter stimuli share common signal transduction components. Transgenic expression of a human TAS2R in sweet or bitter taste receptor-expressing cells of mice induced either strong attraction or aversion to the receptor’s cognate bitter tastant. Thus, dedicated taste receptor cells appear to function as broadly tuned detectors for bitter substances and are wired to elicit aversive behavior.

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References

  • Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS (2000) A novel family of mammalian taste receptors [see comments]. Cell 100:693–702

    PubMed  CAS  Google Scholar 

  • Akabas MH, Dodd J, Al-Awqati Q (1988) A bitter substance induces a rise in intracellular calcium in a subpopulation of rat taste cells. Science 242:1047–1050

    PubMed  CAS  Google Scholar 

  • Ammon C, Schafer J, Kreuzer OJ, Meyerhof W (2002) Presence of a plasma membrane targeting sequence in the amino-terminal region of the rat somatostatin receptor 3. Arch Physiol Biochem 110:137–145

    PubMed  CAS  Google Scholar 

  • Andres-Barquin PJ, Conte C (2004) Molecular basis of bitter taste: the T2R family of G protein-coupled receptors. Cell Biochem Biophys 41:99–112

    PubMed  CAS  Google Scholar 

  • Aspen J, Gatch MB, Woods JH (1999) Training and characterization of a quinine taste discrimination in rhesus monkeys. Psychopharmacology 141:251–257

    PubMed  CAS  Google Scholar 

  • Barnicot NA, Harris H, Kalmus H (1951) Taste thresholds of further eighteen compounds and their correlation with P.T.C thresholds. Ann Eugen 16:119–128

    PubMed  CAS  Google Scholar 

  • Barratt-Fornell A, Drewnowski A (2002) The taste of health: nature’s bitter gifts. Nutr Today 37:144–150

    PubMed  Google Scholar 

  • Bartoshuk LM (2000) Comparing sensory experiences across individuals: recent psychophysical advances illuminate genetic variation in taste perception. Chem Senses 25:447–460

    PubMed  CAS  Google Scholar 

  • Behrens M, Brockhoff A, Kuhn C, Bufe B, Winnig M, Meyerhof W (2004) The human taste receptor hTAS2R14 responds to a variety of different bitter compounds. Biochem Biophys Res Commun 319:479–485

    PubMed  CAS  Google Scholar 

  • Belitz H-D, Wieser H (1985) Bitter compounds: occurrence and structure-activity relationship. Food Rev Int 1:271–354

    CAS  Google Scholar 

  • Biere A, Marak HB, Van Damme JM (2004) Plant chemical defense against herbivores and pathogens: generalized defense or trade-offs? Oecologia 140:430–441

    PubMed  Google Scholar 

  • Bockaert J, Pin JP (1999) Molecular tinkering of G protein-coupled receptors: an evolutionary success. EMBO J 18:1723–1729

    PubMed  CAS  Google Scholar 

  • Bufe B, Hofmann T, Krautwurst D, Raguse JD, Meyerhof W (2002) The human TAS2R16 receptor mediates bitter taste in response to beta-glucopyranosides. Nat Genet 32:397–401

    PubMed  CAS  Google Scholar 

  • Bufe B, Schöley-Pohl E, Krautwurst D, Hofmann T, Meyerhof W (2004) Identification of human bitter taste receptors. Am Chem Soc Symp S 867:45–59

    CAS  Google Scholar 

  • Bufe B, Breslin PA, Kuhn C, Reed DR, Tharp CD, Slack JP, Kim UK, Drayna D, Meyerhof W (2005) The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception. Curr Biol 15:322–327

    PubMed  CAS  Google Scholar 

  • Caicedo A, Roper SD (2001) Taste receptor cells that discriminate between bitter stimuli. Science 291:1557–1560

    PubMed  CAS  Google Scholar 

  • Caicedo A, Kim KN, Roper SD (2002) Individual mouse taste cells respond to multiple chemical stimuli. J Physiol 544:501–509

    PubMed  CAS  Google Scholar 

  • Caicedo A, Pereira E, Margolskee RF, Roper SD (2003) Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter stimuli. J Neurosci 23:9947–9952

    PubMed  CAS  Google Scholar 

  • Chan CY, Yoo JE, Travers SP (2004) Diverse bitter stimuli elicit highly similar patterns of fos-like immunoreactivity in the nucleus of the solitary tract. Chem Senses 29:573–581

    PubMed  CAS  Google Scholar 

  • Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, Guo W, Zuker CS, Ryba NJ (2000) T2Rs function as bitter taste receptors. Cell 100:703–711

    PubMed  CAS  Google Scholar 

  • Clapham DE (2003) TRP channels as cellular sensors. Nature 426:517–524

    PubMed  CAS  Google Scholar 

  • Clapp TR, Stone LM, Margolskee RF, Kinnamon SC (2001) Immunocytochemical evidence for co-expression of type III IP3 receptor with signaling components of bitter taste transduction. BMC Neurosci 2:6

    PubMed  CAS  Google Scholar 

  • Clapp TR, Yang R, Stoick CL, Kinnamon SC, Kinnamon JC (2004) Morphologic characterization of rat taste receptor cells that express components of the phospholipase C signaling pathway. J Comp Neurol 468:311–321

    PubMed  CAS  Google Scholar 

  • Conte C, Ebeling M, Marcuz A, Nef P, Andres-Barquin PJ (2002) Identification and characterization of human taste receptor genes belonging to the TAS2R family. Cytogenet Genome Res 98:45–53

    PubMed  CAS  Google Scholar 

  • Conte C, Ebeling M, Marcuz A, Nef P, Andres-Barquin PJ (2003) Evolutionary relationships of the Tas2r receptor gene families in mouse and human. Physiol Genomics 14:73–82

    PubMed  CAS  Google Scholar 

  • Czepa A, Hofmann T (2003) Structural and sensory characterization of compounds contributing to the bitter off-taste of carrots (Daucus carota L.) and carrot puree. J Agric Food Chem 51:3865–3873

    PubMed  CAS  Google Scholar 

  • Czepa A, Hofmann T (2004) Quantitative studies and sensory analyses on the influence of cultivar, spatial tissue distribution, and industrial processing on the bitter off-taste of carrots (Daucus carota l.) and carrot products. J Agric Food Chem 52:4508–4514

    PubMed  CAS  Google Scholar 

  • Dahl M, Erickson RP, Simon SA (1997) Neural responses to bitter compounds in rats. Brain Res 756:22–34

    PubMed  CAS  Google Scholar 

  • Damak S, Rong M, Yasumatsu K, Kokrashvili Z, Varadarajan V, Zou S, Jiang P, Ninomiya Y, Margolskee RF (2003) Detection of sweet and umami taste in the absence of taste receptor T1r3. Science 301:850–853

    PubMed  CAS  Google Scholar 

  • Danilova V, Hellekant G (2003) Comparison of the responses of the chorda tympani and glossopharyngeal nerves to taste stimuli in C57BL/6J mice. BMC Neurosci 4:5

    PubMed  Google Scholar 

  • Danilova V, Hellekant G (2004) Sense of taste in a New World monkey, the common marmoset. II. Link between behavior and nerve activity. J Neurophysiol 92:1067–1076

    PubMed  Google Scholar 

  • Denton D (1982) The hunger for salt; an anthropological and medical analysis. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Di Lorenzo PM, Lemon CH (2000) The neural code for taste in the nucleus of the solitary tract of the rat: effects of adaptation. Brain Res 852:383–397

    PubMed  Google Scholar 

  • Drayna D, Coon H, Kim UK, Elsner T, Cromer K, Otterud B, Baird L, Peiffer AP, Leppert M (2003) Genetic analysis of a complex trait in the Utah Genetic Reference Project: a major locus for PTC taste ability on chromosome 7q and a secondary locus on chromosome 16p. Hum Genet 6:6

    Google Scholar 

  • Drewnowski A, Gomez-Carneros C (2000) Bitter taste, phytonutrients, and the consumer: a review [in process citation]. Am J Clin Nutr 72:1424–1435

    PubMed  CAS  Google Scholar 

  • Duncan LM, Deeds J, Hunter J, Shao J, Holmgren LM, Woolf EA, Tepper RI, Shyjan AW (1998) Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis. Cancer Res 58:1515–1520

    PubMed  CAS  Google Scholar 

  • Engel E, Septier C, Leconte N, Salles C, Le Quere JL (2001) Determination of taste-active compounds of a bitter Camembert cheese by omission tests. J Dairy Res 68:675–688

    PubMed  CAS  Google Scholar 

  • Finger TE, Bottger B, Hansen A, Anderson KT, Alimohammadi H, Silver WL (2003) Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration. Proc Natl Acad Sci USA 100:8981–8986

    PubMed  CAS  Google Scholar 

  • Fischer A, Gilad Y, Man O, Paabo S (2005) Evolution of bitter taste receptors in humans and apes. Mol Biol Evol 22:432–436

    PubMed  CAS  Google Scholar 

  • Frank O, Hofmann T (2002) Reinvestigation of the chemical structure of bitter-tasting quinizolate and homoquinizolate and studies on their maillard-type formation pathways using suitable (13)c-labeling experiments. J Agric Food Chem 50:6027–6036

    PubMed  CAS  Google Scholar 

  • Ganshirt H (1953) Isolation of aristolochic acid from various Aristolochiaceae and its quantitative determination. Pharmazie 8:584–592

    PubMed  CAS  Google Scholar 

  • Gienapp E, Schröder KL (1975) Struktur und Bittere in der Huluponreihe. Nahrung 19:697–706

    CAS  Google Scholar 

  • Gilbertson TA, Boughter JD Jr, Zhang H, Smith DV (2001) Distribution of gustatory sensitivities in rat taste cells: whole-cell responses to apical chemical stimulation. J Neurosci 21:4931–4941

    PubMed  CAS  Google Scholar 

  • Go Y, Satta Y, Takenaka O, Takahata N (2005) Lineage-specific loss of function of bitter taste receptor genes in humans and non-human primates. Genetics http://dx.doi.org/10.1534/genetics.104.037523

  • Goren-Inbar N, Alperson N, Kislev ME, Simchoni O, Melamed Y, Ben-Nun A, Werker E (2004) Evidence of hominin control of fire at Gesher Benot Ya’aqov, Israel. Science 304:725–727

    PubMed  CAS  Google Scholar 

  • Guo SW, Reed DR (2001) The genetics of phenylthiocarbamide perception. Ann Hum Biol 28:111–142

    PubMed  CAS  Google Scholar 

  • Gutierrez-Rosales F, Rios JJ, Gomez-Rey ML (2003) Main polyphenols in the bitter taste of virgin olive oil. Structural confirmation by on-line high-performance liquid chromatography electrospray ionization mass spectrometry. J Agric Food Chem 51:6021–6025

    PubMed  CAS  Google Scholar 

  • Habibi-Najafi MB, Lee BH (1996) Bitterness in cheese: a review. Crit Rev Food Sci Nutr 36:397–411

    PubMed  CAS  Google Scholar 

  • Hamor GH (1961) Correlation of chemical structure and taste in the saccharin series. Science 131:1416–1417

    Google Scholar 

  • Harris H, Kalmus H (1949) Chemical specificity in genetical differences of taste sensitivity. Ann Eugen 15:32–45

    PubMed  CAS  Google Scholar 

  • He W, Danilova V, Zou S, Hellekant G, Max M, Margolskee RF, Damak S (2002) Partial rescue of taste responses of alpha-gustducin null mice by transgenic expression of alpha-transducin. Chem Senses 27:719–727

    PubMed  CAS  Google Scholar 

  • Hellekant G, Ninomiya Y, Danilova V (1998) Taste in chimpanzees. III. Labeled-line coding in sweet taste. Physiol Behav 65:191–200

    PubMed  CAS  Google Scholar 

  • Hilliard MA, Bergamasco C, Arbucci S, Plasterk RH, Bazzicalupo P (2004) Worms taste bitter: ASH neurons, QUI-1, GPA-3 and ODR-3 mediate quinine avoidance in Caenorhabditis elegans. EMBO J 23:1101–1111

    PubMed  CAS  Google Scholar 

  • Höfer D, Puschel B, Drenckhahn D (1996) Taste receptor-like cells in the rat gut identified by expression of alpha-gustducin. Proc Natl Acad Sci USA 93:6631–6634

    PubMed  Google Scholar 

  • Hofmann T, Chubanov V, Gudermann T, Montell C (2003) TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel. Curr Biol 13:1153–1158

    PubMed  CAS  Google Scholar 

  • Horne J, Lawless HT, Speirs W, Sposato D (2002) Bitter taste of saccharin and acesulfame-K. Chem Senses 27:31–38

    PubMed  CAS  Google Scholar 

  • Huang L, Shanker YG, Dubauskaite J, Zheng JZ, Yan W, Rosenzweig S, Spielman AI, Max M, Margolskee RF (1999) Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium. Nat Neurosci 2:1055–1062

    PubMed  CAS  Google Scholar 

  • Huang YJ, Maruyama Y, Lu KS, Pereira E, Plonsky I, Baur JE, Wu D, Roper SD (2005) Mouse taste buds use serotonin as a neurotransmitter. J Neurosci 25:843–847

    PubMed  CAS  Google Scholar 

  • Hwang PM, Verma A, Bredt DS, Snyder SH (1990) Localization of phosphatidylinositol signaling components in rat taste cells: role in bitter taste transduction. Proc Natl Acad Sci USA 87:7395–7399

    PubMed  CAS  Google Scholar 

  • Jiang P, Cui M, Zhao B, Liu Z, Snyder LA, Benard LM, Osman R, Margolskee RF, Max M (2005) Lactisole interacts with the transmembrane domains of human T1R3 to inhibit sweet taste. J Biol Chem 280:15238–15246

    PubMed  CAS  Google Scholar 

  • Katz A, Wu D, Simon MI (1992) Subunits beta gamma of heterotrimeric G protein activate beta 2 isoform of phospholipase C. Nature 360:686–689

    PubMed  CAS  Google Scholar 

  • Katz DB, Nicolelis MA, Simon SA (2002) Gustatory processing is dynamic and distributed. Curr Opin Neurobiol 12:448–454

    PubMed  CAS  Google Scholar 

  • Keast RS, Breslin PA (2002) Cross-adaptation and bitterness inhibition of l-tryptophan, l-phenylalanine and urea: further support for shared peripheral physiology. Chem Senses 27:123–131

    PubMed  Google Scholar 

  • Kim MR, Kusakabe Y, Miura H, Shindo Y, Ninomiya Y, Hino A (2003a) Regional expression patterns of taste receptors and gustducin in the mouse tongue. Biochem Biophys Res Commun 312:500–506

    PubMed  CAS  Google Scholar 

  • Kim UK, Jorgenson E, Coon H, Leppert M, Risch N, Drayna D (2003b) Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science 299:1221–1225

    PubMed  CAS  Google Scholar 

  • Kingsbury J (1964) Poisonous plants of the United States and Canada. Prentice Hall, Englewood Cliffs

    Google Scholar 

  • Kock K, Morley SD, Mullins JJ, Schmale H (1994) Denatonium bitter tasting among transgenic mice expressing rat von Ebner’s gland protein. Physiol Behav 56:1173–1177

    PubMed  CAS  Google Scholar 

  • Kolesnikov SS, Margolskee RF (1995) A cyclic-nucleotide-suppressible conductance activated by transducin in taste cells. Nature 376:85–88

    PubMed  CAS  Google Scholar 

  • Krautwurst D, Yau KW, Reed RR (1998) Identification of ligands for olfactory receptors by functional expression of a receptor library. Cell 95:917–926

    PubMed  CAS  Google Scholar 

  • Kretz O, Barbry P, Bock R, Lindemann B (1999) Differential expression of RNA and protein of the three pore-forming subunits of the amiloride-sensitive epithelial sodium channel in taste buds of the rat. J Histochem Cytochem 47:51–64

    PubMed  CAS  Google Scholar 

  • Kubo I (1994) Structural basis for bitterness based on Rabdosia diterpenes. Physiol Behav 56:1203–1207

    PubMed  CAS  Google Scholar 

  • Kuhn C, Bufe B, Winnig M, Hofmann T, Frank O, Behrens M, Lewtschenko T, Slack JP, Ward CD, Meyerhof W (2004) Bitter taste receptors for saccharin and acesulfame K. J Neurosci 24:10260–10265

    PubMed  CAS  Google Scholar 

  • Lechtenberg M, Nahrstedt A (1999) Cyanogenic glycosides. In: Ikan R (ed) Naturally occurring glycosides. Wiley, Chichester, pp 147–191

    Google Scholar 

  • Lesschaeve I, Noble AC (2005) Polyphenols: factors influencing their sensory properties and their effects on food and beverage preferences. Am J Clin Nutr 81:330S–335S

    PubMed  CAS  Google Scholar 

  • Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E (2002) Human receptors for sweet and umami taste. Proc Natl Acad Sci USA 99:4692–4696

    PubMed  CAS  Google Scholar 

  • Lindemann B (1996) Taste reception. Physiol Rev 76:718–766

    PubMed  CAS  Google Scholar 

  • Lindemann B (1999) Receptor seeks ligand: on the way to cloning the molecular receptors for sweet and bitter taste. Nat Med 5:381–382 [news]

    PubMed  CAS  Google Scholar 

  • Lindemann B (2001) Receptors and transduction in taste. Nature 413:219–225

    PubMed  CAS  Google Scholar 

  • Liu D, Liman ER (2003) Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proc Natl Acad Sci USA 100:15160–15165

    PubMed  CAS  Google Scholar 

  • Lundy RF Jr, Contreras RJ (1999) Gustatory neuron types in rat geniculate ganglion. J Neurophysiol 82:2970–2988

    PubMed  CAS  Google Scholar 

  • Lush IE (1981) The genetics of tasting in mice. I. Sucrose octaacetate. Genet Res 38:93–95

    PubMed  CAS  Google Scholar 

  • Lush IE (1984) The genetics of tasting in mice. III. Quinine. Genet Res 44:151–160

    PubMed  CAS  Google Scholar 

  • Lush IE (1986) The genetics of tasting in mice. IV. The acetates of raffinose, galactose and beta-lactose. Genet Res 47:117–123

    PubMed  CAS  Google Scholar 

  • Lush IE, Holland G (1988) The genetics of tasting in mice. V. Glycine and cycloheximide. Genet Res 52:207–212

    PubMed  CAS  Google Scholar 

  • Martin JH (1989) Neuroanatomy. Prentice Hall International, London

    Google Scholar 

  • Matsumoto A, Kawaguchi N, Asaka Y, Kubota T (1986) Relationship between lipophilicity, bitterness and structure of phenyl beta-D-glucopyranosides. Food Chem 21:83–92

    CAS  Google Scholar 

  • Matsunami H, Amrein H (2003) Taste and pheromone perception in mammals and flies. Genome Biol 4:220

    PubMed  Google Scholar 

  • Matsunami H, Montmayeur JP, Buck LB (2000) A family of candidate taste receptors in human and mouse. Nature 404:601–604 [see comments]

    PubMed  CAS  Google Scholar 

  • Matsuo R (2000) Role of saliva in the maintenance of taste sensitivity. Crit Rev Oral Biol Med 11:216–229

    PubMed  CAS  Google Scholar 

  • Max M, Shanker YG, Huang L, Rong M, Liu Z, Campagne F, Weinstein H, Damak S, Margolskee RF (2001) Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac. Nat Genet 28:58–63

    PubMed  CAS  Google Scholar 

  • McGregor R (2004) Taste modification in the biotech era. Food Technol 58:24–30

    Google Scholar 

  • McLaughlin SK, McKinnon PJ, Margolskee RF (1992) Gustducin is a taste-cell-specific G protein closely related to the transducins. Nature 357:563–569

    PubMed  CAS  Google Scholar 

  • McLaughlin SK, McKinnon PJ, Spickofsky N, Danho W, Margolskee RF (1994) Molecular cloning of G proteins and phosphodiesterases from rat taste cells. Physiol Behav 56:1157–1164

    PubMed  CAS  Google Scholar 

  • Medler KF, Margolskee RF, Kinnamon SC (2003) Electrophysiological characterization of voltage-gated currents in defined taste cell types of mice. J Neurosci 23:2608–2617

    PubMed  CAS  Google Scholar 

  • Meyerhof W, Kuhn C, Brockhoff A, Winnig M, Bufe B, Schöley-Pohl E, Behrens M (2005) Peripheral receptors and transduction mechanisms in taste perception. In: Hofmann T, Rothe M, Schieberle P (eds) Proceedings of the 8th Wartburg Symposium. State-of-the-art in flavour chemistry and biology. Deutsche Forschungsanstalt für Lebensmittelchemie, Garching

    Google Scholar 

  • Miller IJ Jr (1995) Anatomy of the peripheral taste system. In: Doty RL (ed) Handbook of olfaction and gustation. Dekker, New York, pp 521–547

    Google Scholar 

  • Milton K (2003) The critical role played by animal source foods in human (Homo) evolution. J Nutr 133:3886S–3892S

    PubMed  CAS  Google Scholar 

  • Ming D, Ruiz-Avila L, Margolskee RF (1998) Characterization and solubilization of bitter-responsive receptors that couple to gustducin. Proc Natl Acad Sci USA 95:8933–8938

    PubMed  CAS  Google Scholar 

  • Ming D, Ninomiya Y, Margolskee RF (1999) Blocking taste receptor activation of gustducin inhibits gustatory responses to bitter compounds. Proc Natl Acad Sci USA 96:9903–9908

    PubMed  CAS  Google Scholar 

  • Misaka T, Kusakabe Y, Emori Y, Gonoi T, Arai S, Abe K (1997) Taste buds have a cyclic nucleotide-activated channel, CNGgust. J Biol Chem 272:22623–22629

    PubMed  CAS  Google Scholar 

  • Miwa K, Kanemura F, Tonosaki K (1997) Tastes activate different second messengers in taste cells. J Vet Med Sci 59:81–83

    PubMed  CAS  Google Scholar 

  • Miyoshi MA, Abe K, Emori Y (2001) IP(3) receptor type 3 and PLCbeta2 are co-expressed with taste receptors T1R and T2R in rat taste bud cells. Chem Senses 26:259–265

    PubMed  CAS  Google Scholar 

  • Mombaerts P (2004) Genes and ligands for odorant, vomeronasal and taste receptors. Nat Rev Neurosci 5:263–278

    PubMed  CAS  Google Scholar 

  • Montmayeur JP, Liberles SD, Matsunami H, Buck LB (2001) A candidate taste receptor gene near a sweet taste locus. Nat Neurosci 4:492–498

    PubMed  CAS  Google Scholar 

  • Moriyama M, Oba K (2004) Sprouts as antioxidant food resources and young people’s taste for them. Biofactors 21:247–249

    PubMed  CAS  Google Scholar 

  • Mueller KL, Hoon MA, Erlenbach I, Chandrshekar J, Zuker CS, Ryba NJP (2005) The receptors and coding logic for bitter taste. Nature 434:225–229

    PubMed  CAS  Google Scholar 

  • Murata Y, Sata NU (2000) Isolation and structure of pulcherrimine, a novel bitter-tasting amino acid, from the sea urchin (Hemicentrotus pulcherrimus) ovaries. J Agric Food Chem 48:5557–5560

    PubMed  CAS  Google Scholar 

  • Nakashima K, Ninomiya Y (1998) Increase in inositol 1,4,5-triphosphate levels of the fungiform papilla in response to saccharin and bitter substances in mice. Cell Physiol Biochem 8:224–230

    PubMed  CAS  Google Scholar 

  • Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS (2001) Mammalian sweet taste receptors. Cell 106:381–390

    PubMed  CAS  Google Scholar 

  • Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G, Ryba NJ, Zuker CS (2002) An amino-acid taste receptor. Nature 416:199–202

    PubMed  CAS  Google Scholar 

  • Nishijo H, Norgren R (1997) Parabrachial neural coding of taste stimuli in awake rats. J Neurophysiol 78:2254–2268

    PubMed  CAS  Google Scholar 

  • Nolte DL, Mason JR, Lewis SL (1994) Tolerance of bitter compounds by an herbivore, Cavia porcellus. J Chem Ecol 20:303–308

    CAS  Google Scholar 

  • Northcutt RG (2004) Taste buds: development and evolution. Brain Behav Evol 64:198–206

    PubMed  Google Scholar 

  • Offermanns S, Simon MI (1995) G alpha 15 and G alpha 16 couple a wide variety of receptors to phospholipase C. J Biol Chem 270:15175–15180

    PubMed  CAS  Google Scholar 

  • Ogura T, Mackay-Sim A, Kinnamon SC (1997) Bitter taste transduction of denatonium in the mudpuppy Necturus maculosus. J Neurosci 17:3580–3587

    PubMed  CAS  Google Scholar 

  • Ozeck M, Brust P, Xu H, Servant G (2004) Receptors for bitter, sweet and umami taste couple to inhibitory G protein signaling pathways. Eur J Pharmacol 489:139–149

    PubMed  CAS  Google Scholar 

  • Parry CM, Erkner A, le Coutre J (2004) Divergence of T2R chemosensory receptor families in humans, bonobos, and chimpanzees. Proc Natl Acad Sci USA 101:14830–14834

    PubMed  CAS  Google Scholar 

  • Perez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H, Max M, Margolskee RF (2002) A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci 5:1169–1176

    PubMed  CAS  Google Scholar 

  • Prawitt D, Monteilh-Zoller MK, Brixel L, Spangenberg C, Zabel B, Fleig A, Penner R (2003) TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in [Ca2+]i. Proc Natl Acad Sci USA 100:15166–15171

    PubMed  CAS  Google Scholar 

  • Prodi DA, Drayna D, Forabosco P, Palmas MA, Maestrale GB, Piras D, Pirastu M, Angius A (2004) Bitter taste study in a Sardinian genetic isolate supports the association of phenylthiocarbamide sensitivity to the TAS2R38 bitter receptor gene. Chem Senses 29:697–702

    PubMed  CAS  Google Scholar 

  • Pronin AN, Tang H, Connor J, Keung W (2004) Identification of ligands for two human bitter T2R receptors. Chem Senses 29:583–593

    PubMed  CAS  Google Scholar 

  • Raksakulthai R, Haard NF (2003) Exopeptidases and their application to reduce bitterness in food: a review. Crit Rev Food Sci Nutr 43:401–445

    PubMed  CAS  Google Scholar 

  • Redfern CH, Coward P, Degtyarev MY, Lee EK, Kwa AT, Hennighausen L, Bujard H, Fishman GI, Conklin BR (1999) Conditional expression and signaling of a specifically designed Gi-coupled receptor in transgenic mice. Nat Biotechnol 17:165–169

    PubMed  CAS  Google Scholar 

  • Reed DR, Nanthakumar E, North M, Bell C, Bartoshuk LM, Price RA (1999) Localization of a gene for bitter-taste perception to human chromosome 5p15. Am J Hum Genet 64:1478–1480

    PubMed  CAS  Google Scholar 

  • Rolls ET (1995) Central taste anatomy and neurophysiology. In: Doty RL (eds) Handbook of olfaction and gustation. Dekker, New York, pp 549–573

    Google Scholar 

  • Rolls ET (2004) The functions of the orbitofrontal cortex. Brain Cogn 55:11–29

    PubMed  Google Scholar 

  • Roper SD (1992) The microphysiology of peripheral taste organs. J Neurosci 12:1127–1134

    PubMed  CAS  Google Scholar 

  • Rössler P, Kroner C, Freitag J, Noe J, Breer H (1998) Identification of a phospholipase C beta subtype in rat taste cells. Eur J Cell Biol 77:253–261

    PubMed  Google Scholar 

  • Rossler P, Boekhoff I, Tareilus E, Beck S, Breer H, Freitag J (2000) G protein betagamma complexes in circumvallate taste cells involved in bitter transduction. Chem Senses 25:413–421

    PubMed  CAS  Google Scholar 

  • Rouseff RL (1980) Flavonoids and citrus quality. ACS Symposium Series 143:83–108

    CAS  Google Scholar 

  • Rozin P, Vollmecke TA (1986) Food likes and dislikes. Annu Rev Nutr 6:433–456

    PubMed  CAS  Google Scholar 

  • Ruiz-Avila L, McLaughlin SK, Wildman D, McKinnon PJ, Robichon A, Spickofsky N, Margolskee RF (1995) Coupling of bitter receptor to phosphodiesterase through transducin in taste receptor cells. Nature 376:80–85

    PubMed  CAS  Google Scholar 

  • Ruiz-Avila L, Ming D, Margolskee RF (2000) An in vitro assay useful to determine the potency of several bitter compounds. Chem Senses 25:361–368

    PubMed  CAS  Google Scholar 

  • Saito H, Kubota M, Roberts RW, Chi Q, Matsunami H (2004) RTP family members induce functional expression of mammalian odorant receptors. Cell 119:679–691

    PubMed  CAS  Google Scholar 

  • Saper CB, Chou TC, Elmquist JK (2002) The need to feed: homeostatic and hedonic control of eating. Neuron 36:199–211

    PubMed  CAS  Google Scholar 

  • Saroli A (1984) Structure-activity relationship of a bitter compound: denatonium chloride. Naturwissenschaften 71:428–429

    PubMed  CAS  Google Scholar 

  • Sato T, Beidler LM (1997) Broad tuning of rat taste cells for four basic taste stimuli. Chem Senses 22:287–293

    PubMed  CAS  Google Scholar 

  • Sbarbati A, Osculati F (2003) Solitary chemosensory cells in mammals? Cells Tissues Organs 175:51–55

    PubMed  CAS  Google Scholar 

  • Sbarbati A, Crescimanno C, Bernardi P, Osculati F (1999) Alpha-gustducin-immunoreactive solitary chemosensory cells in the developing chemoreceptorial epithelium of the rat vallate papilla. Chem Senses 24:469–472

    PubMed  CAS  Google Scholar 

  • Sbarbati A, Merigo F, Benati D, Tizzano M, Bernardi P, Osculati F (2004) Laryngeal chemosensory clusters. Chem Senses 29:683–692

    PubMed  CAS  Google Scholar 

  • Schieberle P, Hofmann T (2003) Die molekulare Welt des Lebensmittelgenusses. Chem Unserer Zeit 37:388–401

    CAS  Google Scholar 

  • Schiffman SS (2000) Taste quality and neural coding: implications from psychophysics and neurophysiology. Physiol Behav 69:147–159

    PubMed  CAS  Google Scholar 

  • Schiffman SS, Gatlin CA (1993) Sweeteners: state of knowledge review. Neurosci Biobehav Rev 17:313–345

    PubMed  CAS  Google Scholar 

  • Schiffman SS, Zervakis J, Heffron S, Heald AE (1999) Effect of protease inhibitors on the sense of taste. Nutrition 15:767–772

    PubMed  CAS  Google Scholar 

  • Schmale H, Bamberger C (1997) A novel protein with strong homology to the tumor suppressor p53. Oncogene 15:1363–1367

    PubMed  CAS  Google Scholar 

  • Schmale H, Holtgreve-Grez H, Christiansen H (1990) Possible role for salivary gland protein in taste reception indicated by homology to lipophilic-ligand carrier proteins. Nature 343:366–369

    PubMed  CAS  Google Scholar 

  • Schoenfeld MA, Neuer G, Tempelmann C, Schussler K, Noesselt T, Hopf JM, Heinze HJ (2004) Functional magnetic resonance tomography correlates of taste perception in the human primary taste cortex. Neuroscience 127:347–353

    PubMed  CAS  Google Scholar 

  • Scott TR, Giza BK (2000) Issues of gustatory neural coding: where they stand today. Physiol Behav 69:65–76

    PubMed  CAS  Google Scholar 

  • Scott TR, Giza BK, Yan J (1999) Gustatory neural coding in the cortex of the alert cynomolgus macaque: the quality of bitterness. J Neurophysiol 81:60–71

    PubMed  CAS  Google Scholar 

  • Serafini M, Bugianesi R, Maiani G, Valtuena S, De Santis S, Crozier A (2003) Plasma antioxidants from chocolate. Nature 424:1013

    PubMed  CAS  Google Scholar 

  • Shallenberger RS, Acree TE (1967) Molecular theory of sweet taste. Nature 216:480–482

    PubMed  CAS  Google Scholar 

  • Shi P, Zhang J, Yang H, Zhang YP (2003) Adaptive diversification of bitter taste receptor genes in Mammalian evolution. Mol Biol Evol 20:805–814

    PubMed  CAS  Google Scholar 

  • Shirokova E, Schmiedeberg K, Bedner P, Niessen H, Willecke K, Raguse JD, Meyerhof W, Krautwurst D (2005) Identification of specific ligands for orphan olfactory receptors: G protein-dependent agonism and antagonism of odorants. J Biol Chem 280:11807–11815

    PubMed  CAS  Google Scholar 

  • Smith DV, Frank ME (1993) Sensory coding by peripheral taste fibers. In: Simon SA, Frank ME (eds) Mechanisms of taste transduction. CRC, Boca Raton, pp 295–338

    Google Scholar 

  • Smith DV, St John SJ (1999) Neural coding of gustatory information. Curr Opin Neurobiol 9:427–435

    PubMed  CAS  Google Scholar 

  • Spector AC, Kopka SL (2002) Rats fail to discriminate quinine from denatonium: implications for the neural coding of bitter-tasting compounds. J Neurosci 22:1937–1941

    PubMed  CAS  Google Scholar 

  • Spielman AI, Huque T, Nagai H, Whitney G, Brand JG (1994) Generation of inositol phosphates in bitter taste transduction. Physiol Behav 56:1149–1155

    PubMed  CAS  Google Scholar 

  • Spielman AI, Nagai H, Sunavala G, Dasso M, Breer H, Boekhoff I, Huque T, Whitney G, Brand JG (1996) Rapid kinetics of second messenger production in bitter taste. Am J Physiol 270:C926–C931

    PubMed  CAS  Google Scholar 

  • Steiner JE (1994) Behavior manifestations indicative of hedonics and intensity in chemosensory experience. In: Kurihara K, Suzuki N, Ogawa H (eds) Olfaction and taste XI. Springer, Tokyo, pp 284–287

    Google Scholar 

  • Stevens DR, Seifert R, Bufe B, Muller F, Kremmer E, Gauss R, Meyerhof W, Kaupp UB, Lindemann B (2001) Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli. Nature 413:631–635

    PubMed  CAS  Google Scholar 

  • Straub SG, Mulvaney-Musa J, Yajima H, Weiland GA, Sharp GW (2003) Stimulation of insulin secretion by denatonium, one of the most bitter-tasting substances known. Diabetes 52:356–364

    PubMed  CAS  Google Scholar 

  • Sugino Y, Umemoto A, Mizutani S (2002) Insensitivity to the bitter taste of chloramphenicol: an autosomal recessive trait. Genes Genet Syst 77:59–62

    PubMed  Google Scholar 

  • Suzuki H, Onishi H, Takahashi Y, Iwata M, Machida Y (2003) Development of oral acetaminophen chewable tablets with inhibited bitter taste. Int J Pharm 251:123–132

    PubMed  CAS  Google Scholar 

  • Tabata S, Wada A, Kobayashi T, Nishimura S, Muguruma M, Iwamoto H (2003) Bovine circumvallate taste buds: taste cell structure and immunoreactivity to alpha-gustducin. Anat Rec 271A:217–224

    CAS  Google Scholar 

  • Takami S, Getchell TV, McLaughlin SK, Margolskee RF, Getchell ML (1994) Human taste cells express the G protein alpha-gustducin and neuron-specific enolase. Brain Res Mol Brain Res 22:193–203

    PubMed  CAS  Google Scholar 

  • Tancredi T, Lelj F, Temussi PA (1979) Three-dimensional mapping of the bitter taste receptor site. Chem Senses Flavour 4:259–265

    CAS  Google Scholar 

  • Tepper BJ (1998) 6-n-Propylthiouracil: a genetic marker for taste, with implications for food preference and dietary habits. Am J Hum Genet 63:1271–1276

    PubMed  CAS  Google Scholar 

  • Tobach E, Bellin JS, Das DK (1974) Differences in bitter taste perception in three strains of rats. Behav Genet 4:405–410

    PubMed  CAS  Google Scholar 

  • Travers SP (2002) Quinine and citric acid elicit distinctive Fos-like immunoreactivity in the rat nucleus of the solitary tract. Am J Physiol Regul Integr Comp Physiol 282:R1798–R1810

    PubMed  CAS  Google Scholar 

  • Uchida T, Tanigake A, Miyanaga Y, Matsuyama K, Kunitomo M, Kobayashi Y, Ikezaki H, Taniguchi A (2003) Evaluation of the bitterness of antibiotics using a taste sensor. J Pharm Pharmacol 55:1479–1485

    PubMed  CAS  Google Scholar 

  • Ueda T, Ugawa S, Ishida Y, Shibata Y, Murakami S, Shimada S (2001) Identification of coding single-nucleotide polymorphisms in human taste receptor genes involving bitter tasting. Biochem Biophys Res Commun 285:147–151

    PubMed  CAS  Google Scholar 

  • Ueda T, Ugawa S, Yamamura H, Imaizumi Y, Shimada S (2003) Functional interaction between T2R taste receptors and G-protein {alpha} subunits expressed in taste receptor cells. J Neurosci 23:7376–7380

    PubMed  CAS  Google Scholar 

  • Verhagen JV, Giza BK, Scott TR (2003) Responses to taste stimulation in the ventroposteromedial nucleus of the thalamus in rats. J Neurophysiol 89:265–275

    PubMed  Google Scholar 

  • von Skramlik E (1926) Handbuch der Physiologie der niederen Sinne. Thieme, Leipzig

    Google Scholar 

  • Wang X, Thomas SD, Zhang J (2004) Relaxation of selective constraint and loss of function in the evolution of human bitter taste receptor genes. Hum Mol Genet 13:2671–2678

    PubMed  CAS  Google Scholar 

  • Wetzel CH, Oles M, Wellerdieck C, Kuczkowiak M, Gisselmann G, Hatt H (1999) Specificity and sensitivity of a human olfactory receptor functionally expressed in human embryonic kidney 293 cells and Xenopus laevis oocytes. J Neurosci 19:7426–7433

    PubMed  CAS  Google Scholar 

  • Whitehead MC, Ganchrow JR, Ganchrow D, Yao B (1999) Organization of geniculate and trigeminal ganglion cells innervating single fungiform taste papillae: a study with tetramethylrhodamine dextran amine labeling. Neuroscience 93:931–941

    PubMed  CAS  Google Scholar 

  • Wong GT, Gannon KS, Margolskee RF (1996a) Transduction of bitter and sweet taste by gustducin. Nature 381:796–800

    PubMed  CAS  Google Scholar 

  • Wong GT, Ruiz-Avila L, Ming D, Gannon KS, Margolskee RF (1996b) Biochemical and transgenic analysis of gustducin’s role in bitter and sweet transduction. Cold Spring Harb Symp Quant Biol 61:173–184

    PubMed  CAS  Google Scholar 

  • Wong GT, Ruiz-Avila L, Margolskee RF (1999) Directing gene expression to gustducin-positive taste receptor cells. J Neurosci 19:5802–5809

    PubMed  CAS  Google Scholar 

  • Wooding S, Kim UK, Bamshad MJ, Larsen J, Jorde LB, Drayna D (2004) Natural selection and molecular evolution in PTC, a bitter-taste receptor gene. Am J Hum Genet 74:637–646

    PubMed  CAS  Google Scholar 

  • Wu SV, Rozengurt N, Yang M, Young SH, Sinnett-Smith J, Rozengurt E (2002) Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells. Proc Natl Acad Sci USA 99:2392–2397

    PubMed  CAS  Google Scholar 

  • Yan W, Sunavala G, Rosenzweig S, Dasso M, Brand JG, Spielman AI (2001) Bitter taste transduced by PLC-beta(2)-dependent rise in IP(3) and alpha-gustducin-dependent fall in cyclic nucleotides. Am J Physiol Cell Physiol 280:C742–C751

    PubMed  CAS  Google Scholar 

  • Yang H, Wanner IB, Roper SD, Chaudhari N (1999) An optimized method for in situ hybridization with signal amplification that allows the detection of rare mRNAs. J Histochem Cytochem 47:431–446

    PubMed  CAS  Google Scholar 

  • Zagrobelny M, Bak S, Rasmussen AV, Jorgensen B, Naumann CM, Lindberg Moller B (2004) Cyanogenic glucosides and plant-insect interactions. Phytochemistry 65:293–306

    PubMed  CAS  Google Scholar 

  • Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ (2003) Coding of sweet, bitter, and umami tastes. Different receptor cells sharing similar signaling pathways. Cell 112:293–301

    PubMed  CAS  Google Scholar 

  • Zhao GQ, Zhang Y, Hoon MA, Chandrashekar J, Erlenbach I, Ryba NJ, Zuker CS (2003) The receptors for mammalian sweet and umami taste. Cell 115:255–266

    PubMed  CAS  Google Scholar 

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Acknowledgements

The author thanks Dr. M. Behrens (Potsdam) for providing Fig. 2 and for helpful comments on the manuscript. The editorial assistance of Mrs. M. Lorse is also gratefully acknowledged. Original work carried out in the author’s laboratory and referred to here was supported by a grant from the German Science Foundation (Me 1024/2–2).

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Meyerhof, W. (2005). Elucidation of mammalian bitter taste. In: Reviews of Physiology, Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 154. Springer, Berlin, Heidelberg. https://doi.org/10.1007/s10254-005-0041-0

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