Abstract
The role of bitter taste receptors has changed considerably over the past years. While initially considered to have predominantly, or even exclusively, gustatory functions, numerous recent reports addressed nongustatory actions of TAS2R s. One site of extraoral bitter taste receptor expression is the respiratory system. It was demonstrated that bitter taste receptors are located in the nasal respiratory epithelium, as well as in ciliated cells of lung epithelium, where they affect respiratory functions in response to noxious stimuli. Another site of TAS2R gene expression is the gastrointestinal tract. Here, bitter compounds are suspected to regulate via activation of TAS2Rs metabolic and digestive functions.
The present article focuses on general pharmacological features and signal transduction components of mammalian TAS2Rs and summarizes current knowledge on Tas2r gene function in respiratory and gastrointestinal systems on the expense of a detailed description of gustatory bitter taste perception, which has been the subject of recent reviews.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS (2000) A novel family of mammalian taste receptors. Cell 100:693–702
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
Behrens M, Brockhoff A, Batram C, Kuhn C, Appendino G, Meyerhof W (2009) The human bitter taste receptor hTAS2R50 is activated by the two natural bitter terpenoids andrographolide and amarogentin. J Agric Food Chem 57:9860–9866
Bezencon C, le Coutre J, Damak S (2006) Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells. Chem Senses 32:41–49
Brockhoff A, Behrens M, Massarotti A, Appendino G, Meyerhof W (2007) Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium. J Agric Food Chem 55:6236–6243
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
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
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
Chandrashekar J, Kuhn C, Oka Y, Yarmolinsky DA, Hummler E, Ryba NJ, Zuker CS (2010) The cells and peripheral representation of sodium taste in mice. Nature 464:297–301
Chen MC, Wu SV, Reeve JR Jr, Rozengurt E (2006) Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels. Am J Physiol Cell Physiol 291:C726–C739
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
Damak S, Rong M, Yasumatsu K, Kokrashvili Z, Perez CA, Shigemura N, Yoshida R, Mosinger B Jr, Glendinning JI, Ninomiya Y, Margolskee RF (2006) Trpm5 null mice respond to bitter, sweet, and umami compounds. Chem Senses 31:253–264
Dong D, Jones G, Zhang S (2009) Dynamic evolution of bitter taste receptor genes in vertebrates. BMC Evol Biol 9:12
Dotson CD, Roper SD, Spector AC (2005) PLCbeta2-independent behavioral avoidance of prototypical bitter-tasting ligands. Chem Senses 30:593–600
Dotson CD, Zhang L, Xu H, Shin YK, Vigues S, Ott SH, Elson AE, Choi HJ, Shaw H, Egan JM, Mitchell BD, Li X, Steinle NI, Munger SD (2008) Bitter taste receptors influence glucose homeostasis. PLoS One 3:e3974
Dyer J, Salmon KS, Zibrik L, Shirazi-Beechey SP (2005) Expression of sweet taste receptors of the T1R family in the intestinal tract and enteroendocrine cells. Biochem Soc Trans 33:302–305
Finger TE, St Jeor VL, Kinnamon JC, Silver WL (1990) Ultrastructure of substance P- and CGRP-immunoreactive nerve fibers in the nasal epithelium of rodents. J Comp Neurol 294:293–305
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 U S A 100:8981–8986
Glendinning JI, Yiin YM, Ackroff K, Sclafani A (2008) Intragastric infusion of denatonium conditions flavor aversions and delays gastric emptying in rodents. Physiol Behav 93:757–765
Gulbransen BD, Clapp TR, Finger TE, Kinnamon SC (2008) Nasal solitary chemoreceptor cell responses to bitter and trigeminal stimulants in vitro. J Neurophysiol 99:2929–2937
Hao S, Sternini C, Raybould HE (2008) Role of CCK1 and Y2 receptors in activation of hindbrain neurons induced by intragastric administration of bitter taste receptor ligands. Am J Physiol Regul Integr Comp Physiol 294:R33–R38
Hao S, Dulake M, Espero E, Sternini C, Raybould HE, Rinaman L (2009) Central Fos expression and conditioned flavor avoidance in rats following intragastric administration of bitter taste receptor ligands. Am J Physiol Regul Integr Comp Physiol 296:R528–R536
Hass N, Schwarzenbacher K, Breer H (2007) A cluster of gustducin-expressing cells in the mouse stomach associated with two distinct populations of enteroendocrine cells. Histochem Cell Biol 128:457–471
He W, Yasumatsu K, Varadarajan V, Yamada A, Lem J, Ninomiya Y, Margolskee RF, Damak S (2004) Umami taste responses are mediated by alpha-transducin and alpha-gustducin. J Neurosci 24:7674–7680
Hofer D, Drenckhahn D (1998) Identification of the taste cell G-protein, alpha-gustducin, in brush cells of the rat pancreatic duct system. Histochem Cell Biol 110:303–309
Hofer D, Puschel B, Drenckhahn D (1996) Taste receptor-like cells in the rat gut identified by expression of alpha-gustducin. Proc Natl Acad Sci U S A 93:6631–6634
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
Huang AL, Chen X, Hoon MA, Chandrashekar J, Guo W, Trankner D, Ryba NJ, Zuker CS (2006) The cells and logic for mammalian sour taste detection. Nature 442:934–938
Intelmann D, Batram C, Kuhn C, Haseleu G, Meyerhof W, Hofmann T (2009) Three TAS2R bitter taste receptors mediate the psychophysical responses to bitter compounds of hops (Humulus lupulus L.) and beer. Chem Percept 2:118–132
Ishimaru Y, Inada H, Kubota M, Zhuang H, Tominaga M, Matsunami H (2006) Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor. Proc Natl Acad Sci U S A 103:12569–12574
Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, Kim HH, Xu X, Chan SL, Juhaszova M, Bernier M, Mosinger B, Margolskee RF, Egan JM (2007) Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A 104:15069–15074
Jeon TI, Zhu B, Larson JL, Osborne TF (2008) SREBP-2 regulates gut peptide secretion through intestinal bitter taste receptor signaling in mice. J Clin Invest 118:3693–3700
Kaji I, Karaki S, Fukami Y, Terasaki M, Kuwahara A (2009) Secretory effects of a luminal bitter tastant and expressions of bitter taste receptors, T2Rs, in the human and rat large intestine. Am J Physiol Gastrointest Liver Physiol 296:G971–G981
Kim UK, Jorgenson E, Coon H, Leppert M, Risch N, Drayna D (2003) Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science 299:1221–1225
Kokrashvili Z, Mosinger B, Margolskee RF (2009) Taste signaling elements expressed in gut enteroendocrine cells regulate nutrient-responsive secretion of gut hormones. Am J Clin Nutr 90:822S–825S
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
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
Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E (2002) Human receptors for sweet and umami taste. Proc Natl Acad Sci U S A 99:4692–4696
Lin W, Ogura T, Margolskee RF, Finger TE, Restrepo D (2008) TRPM5-expressing solitary chemosensory cells respond to odorous irritants. J Neurophysiol 99:1451–1460
Little TJ, Gupta N, Case RM, Thompson DG, McLaughlin JT (2009) Sweetness and bitterness taste of meals per se does not mediate gastric emptying in humans. Am J Physiol Regul Integr Comp Physiol 297:R632–R639
Liu L, Simon SA (2000) Capsaicin, acid and heat-evoked currents in rat trigeminal ganglion neurons: relationship to functional VR1 receptors. Physiol Behav 69:363–378
LopezJimenez ND, Cavenagh MM, Sainz E, Cruz-Ithier MA, Battey JF, Sullivan SL (2006) Two members of the TRPP family of ion channels, Pkd1l3 and Pkd2l1, are co-expressed in a subset of taste receptor cells. J Neurochem 98:68–77
Maehashi K, Matano M, Wang H, Vo LA, Yamamoto Y, Huang L (2008) Bitter peptides activate hTAS2Rs, the human bitter receptors. Biochem Biophys Res Commun 365:851–855
Margolskee RF (2002) Molecular mechanisms of bitter and sweet taste transduction. J Biol Chem 277:1–4
Margolskee RF, Dyer J, Kokrashvili Z, Salmon KS, Ilegems E, Daly K, Maillet EL, Ninomiya Y, Mosinger B, Shirazi-Beechey SP (2007) T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proc Natl Acad Sci U S A 104:15075–15080
Matsunami H, Montmayeur JP, Buck LB (2000) A family of candidate taste receptors in human and mouse. Nature 404:601–604
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
McKemy DD, Neuhausser WM, Julius D (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416:52–58
McLaughlin SK, McKinnon PJ, Margolskee RF (1992) Gustducin is a taste-cell-specific G protein closely related to the transducins. Nature 357:563–569
Meyerhof W, Batram C, Kuhn C, Brockhoff A, Chudoba E, Bufe B, Appendino G, Behrens M (2010) The molecular receptive ranges of human TAS2R bitter taste receptors. Chem Senses 35:157–170
Montmayeur JP, Liberles SD, Matsunami H, Buck LB (2001) A candidate taste receptor gene near a sweet taste locus. Nat Neurosci 4:492–498
Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS (2001) Mammalian sweet taste receptors. Cell 106:381–390
Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G, Ryba NJ, Zuker CS (2002) An amino-acid taste receptor. Nature 416:199–202
Ogura T, Mackay-Sim A, Kinnamon SC (1997) Bitter taste transduction of denatonium in the mudpuppy Necturus maculosus. J Neurosci 17:3580–3587
Pronin AN, Tang H, Connor J, Keung W (2004) Identification of ligands for two human bitter T2R receptors. Chem Senses 29:583–593
Pronin AN, Xu H, Tang H, Zhang L, Li Q, Li X (2007) Specific alleles of bitter receptor genes influence human sensitivity to the bitterness of aloin and saccharin. Curr Biol 17:1403–1408
Rossler 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
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
Rozengurt N, Wu SV, Chen MC, Huang C, Sternini C, Rozengurt E (2006) Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon. Am J Physiol Gastrointest Liver Physiol 291:G792–802
Sainz E, Cavenagh MM, Gutierrez J, Battey JF, Northup JK, Sullivan SL (2007) Functional characterization of human bitter taste receptors. Biochem J 403:537–543
Saitoh O, Hirano A, Nishimura Y (2007) Intestinal STC-1 cells respond to five basic taste stimuli. Neuroreport 18:1991–1995
Sbarbati A, Osculati F (2005) A new fate for old cells: brush cells and related elements. J Anat 206:349–358
Shah AS, Ben-Shahar Y, Moninger TO, Kline JN, Welsh MJ (2009) Motile cilia of human airway epithelia are chemosensory. Science 325:1131–1134
Stahler F, Riedel K, Demgensky S, Neumann K, Dunkel A, Taubert A, Raab B, Behrens M, Raguse JD, Hofmann T, Meyerhof W (2008) A role of the epithelial sodium channel in human salt taste transduction? Chem Percept 1:78–90
Sternini C, Anselmi L, Rozengurt E (2008) Enteroendocrine cells: a site of ‘taste’ in gastrointestinal chemosensing. Curr Opin Endocrinol Diabetes Obes 15:73–78
Sutherland K, Young RL, Cooper NJ, Horowitz M, Blackshaw LA (2007) Phenotypic characterization of taste cells of the mouse small intestine. Am J Physiol Gastrointest Liver Physiol 292:G1420–G1428
Talavera K, Yasumatsu K, Voets T, Droogmans G, Shigemura N, Ninomiya Y, Margolskee RF, Nilius B (2005) Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature 438:1022–1025
Tizzano M, Gulbransen BD, Vandenbeuch A, Clapp TR, Herman JP, Sibhatu HM, Churchill ME, Silver WL, Kinnamon SC, Finger TE (2010) Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Proc Natl Acad Sci U S A 107:3210–3215
Wicks D, Wright J, Rayment P, Spiller R (2005) Impact of bitter taste on gastric motility. Eur J Gastroenterol Hepatol 17:961–965
Wong GT, Gannon KS, Margolskee RF (1996) Transduction of bitter and sweet taste by gustducin. Nature 381:796–800
Wong GT, Ruiz-Avila L, Margolskee RF (1999) Directing gene expression to gustducin-positive taste receptor cells. J Neurosci 19:5802–5809
Wooding S, Bufe B, Grassi C, Howard MT, Stone AC, Vazquez M, Dunn DM, Meyerhof W, Weiss RB, Bamshad MJ (2006) Independent evolution of bitter-taste sensitivity in humans and chimpanzees. Nature 440:930–934
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 U S A 99:2392–2397
Wu SV, Chen MC, Rozengurt E (2005) Genomic organization, expression, and function of bitter taste receptors (T2R) in mouse and rat. Physiol Genomics 22:139–149
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
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Berlin Heidelberg
About this chapter
Cite this chapter
Behrens, M., Meyerhof, W. (2011). Oral and Extraoral Bitter Taste Receptors. In: Meyerhof, W., Beisiegel, U., Joost, HG. (eds) Sensory and Metabolic Control of Energy Balance. Results and Problems in Cell Differentiation, vol 52. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-14426-4_8
Download citation
DOI: https://doi.org/10.1007/978-3-642-14426-4_8
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-14425-7
Online ISBN: 978-3-642-14426-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)