The pharmacology of bitter taste receptors and their role in human airways

Pharmacology and Therapeutics

Volumn 155, Issue , 2015, Pages 11-21

  Devillier, Philippe ^a   Naline, Emmanuel ^a   Grassin Delyle, Stanislas ^a  

^a LABORATOIRE DES SCIENCES DU CLIMAT ET DE L ENVIRONNEMENT   (France)

Author keywords

Airways; Bitter taste receptors

Indexed keywords

G PROTEIN COUPLED RECEPTOR; RECEPTOR SUBTYPE; TASTE RECEPTORS, TYPE 2;

AGONIST; AIRWAY; BITTER TASTE; HUMAN; OLIGOMERIZATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; RECEPTOR DOWN REGULATION; REVIEW; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; STRUCTURE ACTIVITY RELATION; TASTE BUD; ANIMAL; METABOLISM; RESPIRATORY SYSTEM; RESPIRATORY TRACT DISEASE;

ANIMALS; HUMANS; RECEPTORS, G-PROTEIN-COUPLED; RESPIRATORY SYSTEM; RESPIRATORY TRACT DISEASES;

EID: 84945486808     PISSN: 01637258     EISSN: 1879016X     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2015.08.001     Document Type: Review

References (134)

1. N.D. Adappa, T.J. Howland, J.N. Palmer, D.W. Kennedy, L. Doghramji, A. Lysenko, D.R. Reed, R.J. Lee, and N.A. Cohen Genetics of the taste receptor T2R38 correlates with chronic rhinosinusitis necessitating surgical intervention Int Forum Allergy Rhinol 3 2013 184 187
2. N.D. Adappa, Z. Zhang, J.N. Palmer, D.W. Kennedy, L. Doghramji, A. Lysenko, D.R. Reed, T. Scott, N.W. Zhao, D. Owens, R.J. Lee, and N.A. Cohen The bitter taste receptor T2R38 is an independent risk factor for chronic rhinosinusitis requiring sinus surgery Int Forum Allergy Rhinol 4 2014 3 7
3. E. Adler, M.A. Hoon, K.L. Mueller, J. Chandrashekar, N.J. Ryba, and C.S. Zuker A novel family of mammalian taste receptors Cell 100 2000 693 702
4. M.H. Akabas, J. Dodd, and Q. Al-Awqati A bitter substance induces a rise in intracellular calcium in a subpopulation of rat taste cells Science 242 1988 1047 1050
5. S.S. An, K.S. Robinett, D.A. Deshpande, W.C. Wang, and S.B. Liggett Reply to: activation of BK channels may not be required for bitter tastant-induced bronchodilation Nat Med 18 2012 650 651
6. S.S. An, W.C. Wang, C.J. Koziol-White, K. Ahn, D.Y. Lee, R.C. Kurten, R.A. Panettieri Jr., and S.B. Liggett TAS2R activation promotes airway smooth muscle relaxation despite beta(2)-adrenergic receptor tachyphylaxis Am J Physiol Lung Cell Mol Physiol 303 2012 L304 L311
7. P.J. Andres-Barquin, and C. Conte Molecular basis of bitter taste: the T2R family of G protein-coupled receptors Cell Biochem Biophys 41 2004 99 112
8. M. Aoki, T. Takao, K. Takao, F. Koike, and N. Suganuma Lower expressions of the human bitter taste receptor TAS2R in smokers: reverse transcriptase-polymerase chain reaction analysis Tob Induc Dis 12 2014 12
9. H.P. Barham, S.E. Cooper, C.B. Anderson, M. Tizzano, T.T. Kingdom, T.E. Finger, S.C. Kinnamon, and V.R. Ramakrishnan Solitary chemosensory cells and bitter taste receptor signaling in human sinonasal mucosa Int Forum Allergy Rhinol 3 2013 450 457
10. M. Behrens, A. Brockhoff, C. Kuhn, B. Bufe, M. Winnig, and W. Meyerhof The human taste receptor hTAS2R14 responds to a variety of different bitter compounds Biochem Biophys Res Commun 319 2004 479 485
11. M. Behrens, H.C. Gunn, P.C. Ramos, W. Meyerhof, and S.P. Wooding Genetic, functional, and phenotypic diversity in TAS2R38-mediated bitter taste perception Chem Senses 38 2013 475 484
12. M. Behrens, and W. Meyerhof Bitter taste receptor research comes of age: from characterization to modulation of TAS2Rs Semin Cell Dev Biol 24 2013 215 221
13. M.G. Belvisi, N. Dale, M.A. Birrell, and B.J. Canning Bronchodilator activity of bitter tastants in human tissue Nat Med 17 2011 776 (author reply 776-778)
14. X. Biarnes, A. Marchiori, A. Giorgetti, C. Lanzara, P. Gasparini, P. Carloni, S. Born, A. Brockhoff, M. Behrens, and W. Meyerhof Insights into the binding of phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor PLoS One 5 2010 e12394
15. M.C. Bohin, W.S. Roland, H. Gruppen, R.J. Gouka, H.T. van der Hijden, P. Dekker, G. Smit, and J.P. Vincken Evaluation of the bitter-masking potential of food proteins for EGCG by a cell-based human bitter taste receptor assay and binding studies J Agric Food Chem 61 2013 10010 10017
16. S. Born, A. Levit, M.Y. Niv, W. Meyerhof, and M. Behrens The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands J Neurosci 33 2013 201 213
17. J.E. Bourke, C. Donovan, M. FitzPatrick, and M. Simoons Bitter taste receptor agonists are novel bronchodilators of small airways in mouse lung slices Am J Respir Crit Care Med 187 2013 A2288
18. T. Braun, B. Mack, and M.F. Kramer Solitary chemosensory cells in the respiratory and vomeronasal epithelium of the human nose: a pilot study Rhinology 49 2011 507 512
19. A. Brockhoff, M. Behrens, A. Massarotti, G. Appendino, and W. Meyerhof 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 2007 6236 6243
20. A. Brockhoff, M. Behrens, M.Y. Niv, and W. Meyerhof Structural requirements of bitter taste receptor activation Proc Natl Acad Sci U S A 107 2010 11110 11115
21. A. Brockhoff, M. Behrens, N. Roudnitzky, G. Appendino, C. Avonto, and W. Meyerhof Receptor agonism and antagonism of dietary bitter compounds J Neurosci 31 2011 14775 14782
22. B. Bufe, P.A. Breslin, C. Kuhn, D.R. Reed, C.D. Tharp, J.P. Slack, U.K. Kim, D. Drayna, and W. Meyerhof The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception Curr Biol 15 2005 322 327
23. B. Bufe, T. Hofmann, D. Krautwurst, J.D. Raguse, and W. Meyerhof The human TAS2R16 receptor mediates bitter taste in response to beta-glucopyranosides Nat Genet 32 2002 397 401
24. A. Caicedo, E. Pereira, R.F. Margolskee, and S.D. Roper Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter stimuli J Neurosci 23 2003 9947 9952
25. M.C. Campbell, A. Ranciaro, D. Zinshteyn, R. Rawlings-Goss, J. Hirbo, S. Thompson, D. Woldemeskel, A. Froment, J.B. Rucker, S.A. Omar, J.M. Bodo, T. Nyambo, G. Belay, D. Drayna, P.A. Breslin, and S.A. Tishkoff Origin and differential selection of allelic variation at TAS2R16 associated with salicin bitter taste sensitivity in Africa Mol Biol Evol 31 2014 288 302
26. J. Chandrashekar, M.A. Hoon, N.J. Ryba, and C.S. Zuker The receptors and cells for mammalian taste Nature 444 2006 288 294
27. J. Chandrashekar, K.L. Mueller, M.A. Hoon, E. Adler, L. Feng, W. Guo, C.S. Zuker, and N.J. Ryba T2Rs function as bitter taste receptors Cell 100 2000 703 711
28. T.R. Clapp, L.M. Stone, R.F. Margolskee, and S.C. Kinnamon Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction BMC Neurosci 2 2001 6
29. T.R. Clapp, K.R. Trubey, A. Vandenbeuch, L.M. Stone, R.F. Margolskee, N. Chaudhari, and S.C. Kinnamon Tonic activity of Galpha-gustducin regulates taste cell responsivity FEBS Lett 582 2008 3783 3787
30. S.P. Cohen, B.K. Buckley, M. Kosloff, A.L. Garland, D.E. Bosch, G. Cheng Jr., H. Radhakrishna, M.D. Brown, F.S. Willard, V.Y. Arshavsky, R. Tarran, D.P. Siderovski, and A.J. Kimple Regulator of G-protein signaling-21 (RGS21) is an inhibitor of bitter gustatory signaling found in lingual and airway epithelia J Biol Chem 287 2012 41706 41719
31. C. Conte, M. Ebeling, A. Marcuz, P. Nef, and P.J. Andres-Barquin Identification and characterization of human taste receptor genes belonging to the TAS2R family Cytogenet Genome Res 98 2002 45 53
32. G. Corder, S. Doolen, R.R. Donahue, M.K. Winter, B.L. Jutras, Y. He, X. Hu, J.S. Wieskopf, J.S. Mogil, D.R. Storm, Z.J. Wang, K.E. McCarson, and B.K. Taylor Constitutive mu-opioid receptor activity leads to long-term endogenous analgesia and dependence Science 341 2013 1394 1399
33. N. Damann, T. Voets, and B. Nilius TRPs in our senses Curr Biol 18 2008 R880 R889
34. O. Dehkordi, J.E. Rose, K.V. Balan, R.M. Millis, B. Bhatti, and A. Jayam-Trouth Co-expression of nAChRs and molecules of the bitter taste transduction pathway by epithelial cells of intrapulmonary airways Life Sci 86 2010 281 288
35. D.A. Deshpande, W.C. Wang, E.L. McIlmoyle, K.S. Robinett, R.M. Schillinger, S.S. An, J.S. Sham, and S.B. Liggett Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction Nat Med 16 2010 1299 1304
36. M. Ekoff, J.H. Choi, A. James, B. Dahlen, G. Nilsson, and S.E. Dahlen Bitter taste receptor (TAS2R) agonists inhibit IgE-dependent mast cell activation J Allergy Clin Immunol 134 2014 475 478
37. S.S. Ferguson Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling Pharmacol Rev 53 2001 1 24
38. T.E. Finger, B. Bottger, A. Hansen, K.T. Anderson, H. Alimohammadi, and W.L. Silver Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration Proc Natl Acad Sci U S A 100 2003 8981 8986
39. J.N. Fletcher, A.D. Kinghorn, J.P. Slack, T.S. McCluskey, A. Odley, and Z. Jia In vitro evaluation of flavonoids from Eriodictyon californicum for antagonist activity against the bitterness receptor hTAS2R31 J Agric Food Chem 59 2011 13117 13121
40. S. Grassin-Delyle, C. Abrial, M. Brollo, S. Fayad-Kobeissi, E. Naline, and P. Devillier Characterization of the expression and the role of bitter taste receptors in human lung parenchyma and macrophages Am J Respir Crit Care Med 189 2014 A5749
41. S. Grassin-Delyle, C. Abrial, S. Fayad-Kobeissi, M. Brollo, C. Faisy, J.C. Alvarez, E. Naline, and P. Devillier The expression and relaxant effect of bitter taste receptors in human bronchi Respir Res 14 2013 134
42. S. Grassin-Delyle, E. Naline, and P. Devillier Taste receptors in asthma Curr Opin Allergy Clin Immunol 15 2015 63 69
43. T.A. Greene, S. Alarcon, A. Thomas, E. Berdougo, B.J. Doranz, P.A. Breslin, and J.B. Rucker Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin PLoS One 6 2011 e20123
44. B.D. Gulbransen, T.R. Clapp, T.E. Finger, and S.C. Kinnamon Nasal solitary chemoreceptor cell responses to bitter and trigeminal stimulants in vitro J Neurophysiol 99 2008 2929 2937
45. J.E. Hayes, M.R. Wallace, V.S. Knopik, D.M. Herbstman, L.M. Bartoshuk, and V.B. Duffy Allelic variation in TAS2R bitter receptor genes associates with variation in sensations from and ingestive behaviors toward common bitter beverages in adults Chem Senses 36 2011 311 319
46. HGNC. and H.G.N.C., and HGNC Database EMBL Outstation - Hinxton, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SD, UK 2015
47. A. Hochheimer, M. Krohn, K. Rudert, K. Riedel, S. Becker, C. Thirion, and H. Zinke Endogenous gustatory responses and gene expression profile of stably proliferating human taste cells isolated from fungiform papillae Chem Senses 39 2014 359 377
48. T. Hofmann, V. Chubanov, T. Gudermann, and C. Montell TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel Curr Biol 13 2003 1153 1158
49. A.C. Howlett, P.H. Reggio, S.R. Childers, R.E. Hampson, N.M. Ulloa, and D.G. Deutsch Endocannabinoid tone versus constitutive activity of cannabinoid receptors Br J Pharmacol 163 2011 1329 1343
50. A.L. Huang, X. Chen, M.A. Hoon, J. Chandrashekar, W. Guo, D. Trankner, N.J. Ryba, and C.S. Zuker The cells and logic for mammalian sour taste detection Nature 442 2006 934 938
51. L. Huang, Y.G. Shanker, J. Dubauskaite, J.Z. Zheng, W. Yan, S. Rosenzweig, A.I. Spielman, M. Max, and R.F. Margolskee Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium Nat Neurosci 2 1999 1055 1062
52. M. Ji, X. Su, X. Su, Y. Chen, W. Huang, J. Zhang, Z. Gao, C. Li, and X. Lu Identification of novel compounds for human bitter taste receptors Chem Biol Drug Des 84 2014 63 74
53. T. Kenakin, and M. Williams Defining and characterizing drug/compound function Biochem Pharmacol 87 2014 40 63
54. U.K. Kim, E. Jorgenson, H. Coon, M. Leppert, N. Risch, and D. Drayna Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide Science 299 2003 1221 1225
55. U. Kim, S. Wooding, D. Ricci, L.B. Jorde, and D. Drayna Worldwide haplotype diversity and coding sequence variation at human bitter taste receptor loci Hum Mutat 26 2005 199 204
56. S.C. Kinnamon Taste receptor signalling - from tongues to lungs Acta Physiol (Oxf) 204 2012 158 168
57. G. Krasteva, B.J. Canning, P. Hartmann, T.Z. Veres, T. Papadakis, C. Muhlfeld, K. Schliecker, Y.N. Tallini, A. Braun, H. Hackstein, N. Baal, E. Weihe, B. Schutz, M. Kotlikoff, I. Ibanez-Tallon, and W. Kummer Cholinergic chemosensory cells in the trachea regulate breathing Proc Natl Acad Sci U S A 108 2011 9478 9483
58. C. Kuhn, B. Bufe, C. Batram, and W. Meyerhof Oligomerization of TAS2R bitter taste receptors Chem Senses 35 2010 395 406
59. C. Kuhn, B. Bufe, M. Winnig, T. Hofmann, O. Frank, M. Behrens, T. Lewtschenko, J.P. Slack, C.D. Ward, and W. Meyerhof Bitter taste receptors for saccharin and acesulfame K J Neurosci 24 2004 10260 10265
60. Y. Kusakabe, A. Yasuoka, M. Asano-Miyoshi, K. Iwabuchi, I. Matsumoto, S. Arai, Y. Emori, and K. Abe Comprehensive study on G protein alpha-subunits in taste bud cells, with special reference to the occurrence of Galphai2 as a major Galpha species Chem Senses 25 2000 525 531
61. M. Ledda, Z. Kutalik, M.C. Souza Destito, M.M. Souza, C.A. Cirillo, A. Zamboni, N. Martin, E. Morya, K. Sameshima, J.S. Beckmann, J. le Coutre, S. Bergmann, and U.K. Genick GWAS of human bitter taste perception identifies new loci and reveals additional complexity of bitter taste genetics Hum Mol Genet 23 2014 259 267
62. R.J. Lee, B. Chen, K.M. Redding, R.F. Margolskee, and N.A. Cohen Mouse nasal epithelial innate immune responses to Pseudomonas aeruginosa quorum-sensing molecules require taste signaling components Innate Immun 20 2013 606 617
63. R.J. Lee, and N.A. Cohen Bitter and sweet taste receptors in the respiratory epithelium in health and disease J Mol Med (Berl) 92 12 2014 1235 1244
64. R.J. Lee, and N.A. Cohen Sinonasal solitary chemosensory cells "taste" the upper respiratory environment to regulate innate immunity Am J Rhinol Allergy 28 2014 366 373
65. R.J. Lee, and N.A. Cohen Taste receptors in innate immunity Cell Mol Life Sci 72 2 2014 217 236
66. R.J. Lee, and N.A. Cohen Role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis Curr Opin Allergy Clin Immunol 15 1 2015 14 20
67. R.J. Lee, J.M. Kofonow, P.L. Rosen, A.P. Siebert, B. Chen, L. Doghramji, G. Xiong, N.D. Adappa, J.N. Palmer, D.W. Kennedy, J.L. Kreindler, R.F. Margolskee, and N.A. Cohen Bitter and sweet taste receptors regulate human upper respiratory innate immunity J Clin Invest 124 2014 1393 1405
68. R.J. Lee, G. Xiong, J.M. Kofonow, B. Chen, A. Lysenko, P. Jiang, V. Abraham, L. Doghramji, N.D. Adappa, J.N. Palmer, D.W. Kennedy, G.K. Beauchamp, P.T. Doulias, H. Ischiropoulos, J.L. Kreindler, D.R. Reed, and N.A. Cohen T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection J Clin Invest 122 2012 4145 4159
69. A. Levit, S. Nowak, M. Peters, A. Wiener, W. Meyerhof, M. Behrens, and M.Y. Niv The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14 FASEB J 28 2014 1181 1197
70. J.P. Ley, G. Krammer, G. Reinders, I.L. Gatfield, and H.J. Bertram Evaluation of bitter masking flavanones from Herba Santa (Eriodictyon californicum (H. and A.) Torr., Hydrophyllaceae) J Agric Food Chem 53 2005 6061 6066
71. S.V. Lipchock, J.A. Mennella, A.I. Spielman, and D.R. Reed Human bitter perception correlates with bitter receptor messenger RNA expression in taste cells Am J Clin Nutr 98 2013 1136 1143
72. K. Maehashi, M. Matano, H. Wang, L.A. Vo, Y. Yamamoto, and L. Huang Bitter peptides activate hTAS2Rs, the human bitter receptors Biochem Biophys Res Commun 365 2008 851 855
73. A. Malki, J. Fiedler, K. Fricke, I. Ballweg, M.W. Pfaffl, and D. Krautwurst Class I odorant receptors, TAS1R and TAS2R taste receptors, are markers for subpopulations of circulating leukocytes J Leukoc Biol 97 3 2015 533 545
74. J.E. Mangold, T.J. Payne, J.Z. Ma, G. Chen, and M.D. Li Bitter taste receptor gene polymorphisms are an important factor in the development of nicotine dependence in African Americans J Med Genet 45 2008 578 582
75. M.L. Manson, J. Safholm, M. Al-Ameri, P. Bergman, A.C. Orre, K. Sward, A. James, S.E. Dahlen, and M. Adner Bitter taste receptor agonists mediate relaxation of human and rodent vascular smooth muscle Eur J Pharmacol 740C 2014 302 311
76. A. Marchiori, L. Capece, A. Giorgetti, P. Gasparini, M. Behrens, P. Carloni, and W. Meyerhof Coarse-grained/molecular mechanics of the TAS2R38 bitter taste receptor: experimentally-validated detailed structural prediction of agonist binding PLoS One 8 2013 e64675
77. H. Matsunami, J.P. Montmayeur, and L.B. Buck A family of candidate taste receptors in human and mouse Nature 404 2000 601 604
78. S.K. McLaughlin, P.J. McKinnon, and R.F. Margolskee Gustducin is a taste-cell-specific G protein closely related to the transducins Nature 357 1992 563 569
79. J.A. Mennella, M.Y. Pepino, F.F. Duke, and D.R. Reed Age modifies the genotype-phenotype relationship for the bitter receptor TAS2R38 BMC Genet 11 2010 60
80. W. Meyerhof, C. Batram, C. Kuhn, A. Brockhoff, E. Chudoba, B. Bufe, G. Appendino, and M. Behrens The molecular receptive ranges of human TAS2R bitter taste receptors Chem Senses 35 2010 157 170
81. W. Meyerhof, M. Behrens, A. Brockhoff, B. Bufe, and C. Kuhn Human bitter taste perception Chem Senses 30 Suppl. 1 2005 i14 i15
82. L. Mfuna Endam, A. Filali-Mouhim, P. Boisvert, L.P. Boulet, Y. Bosse, and M. Desrosiers Genetic variations in taste receptors are associated with chronic rhinosinusitis: a replication study Int Forum Allergy Rhinol 4 2014 200 206
83. K.P. Minneman Heterodimerization and surface localization of G protein coupled receptors Biochem Pharmacol 73 2007 1043 1050
84. A.H. Morice, R.T. Bennett, M.A. Chaudhry, M.E. Cowen, S.C. Griffin, and M. Loubani Effect of bitter tastants on human bronchi Nat Med 17 2011 775
85. H.R. Moskowitz, V. Kumraiah, K.N. Sharma, H.L. Jacobs, and S.D. Sharma Effects of hunger, satiety and glucose load upon taste intensity and taste hedonics Physiol Behav 16 1976 471 475
86. K.L. Mueller, M.A. Hoon, I. Erlenbach, J. Chandrashekar, C.S. Zuker, and N.J. Ryba The receptors and coding logic for bitter taste Nature 434 2005 225 229
87. K.C. Murray, A. Nakae, M.J. Stephens, M. Rank, J. D'Amico, P.J. Harvey, X. Li, R.L. Harris, E.W. Ballou, R. Anelli, C.J. Heckman, T. Mashimo, R. Vavrek, L. Sanelli, M.A. Gorassini, D.J. Bennett, and K. Fouad Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT2C receptors Nat Med 16 2010 694 700
88. M. Naim, R. Seifert, B. Nurnberg, L. Grunbaum, and G. Schultz Some taste substances are direct activators of G-proteins Biochem J 297 Pt 3 1994 451 454
89. S. Nijmeijer, R. Leurs, and H.F. Vischer Constitutive activity of the histamine H(1) receptor Methods Enzymol 484 2010 127 147
90. T. Ogura, and S.C. Kinnamon IP(3)-Independent release of Ca(2+) from intracellular stores: a novel mechanism for transduction of bitter stimuli J Neurophysiol 82 1999 2657 2666
91. C. Orsmark-Pietras, A. James, J.R. Konradsen, B. Nordlund, C. Soderhall, V. Pulkkinen, C. Pedroletti, K. Daham, M. Kupczyk, B. Dahlen, J. Kere, S.E. Dahlen, G. Hedlin, and E. Melen Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics Eur Respir J 42 2013 65 78
92. A. Panebra, A. Hershfeld, and D.A. Deshpande Bitter taste receptor (BTR) agonists inhibit mitogenic signaling in human airway smooth muscle (ASM) cells Am J Respir Crit Care Med 189 2014 A1047
93. C.A. Perez, L. Huang, M. Rong, J.A. Kozak, A.K. Preuss, H. Zhang, M. Max, and R.F. Margolskee A transient receptor potential channel expressed in taste receptor cells Nat Neurosci 5 2002 1169 1176
94. N. Pirastu, M. Kooyman, M. Traglia, A. Robino, S.M. Willems, G. Pistis, P. d'Adamo, N. Amin, A. d'Eustacchio, L. Navarini, C. Sala, L.C. Karssen, C. van Duijn, D. Toniolo, and P. Gasparini Association analysis of bitter receptor genes in five isolated populations identifies a significant correlation between TAS2R43 variants and coffee liking PLoS One 9 2014 e92065
95. A.N. Pronin, H. Tang, J. Connor, and W. Keung Identification of ligands for two human bitter T2R receptors Chem Senses 29 2004 583 593
96. V. Pulkkinen, M.L. Manson, J. Safholm, M. Adner, and S.E. Dahlen The bitter taste receptor (TAS2R) agonists denatonium and chloroquine display distinct patterns of relaxation of the guinea pig trachea Am J Physiol Lung Cell Mol Physiol 303 2012 L956 L966
97. S.P. Pydi, R.P. Bhullar, and P. Chelikani Constitutively active mutant gives novel insights into the mechanism of bitter taste receptor activation J Neurochem 122 2012 537 544
98. S.P. Pydi, R.P. Bhullar, and P. Chelikani Constitutive activity of bitter taste receptors (T2Rs) Adv Pharmacol 70 2014 303 326
99. S.P. Pydi, N. Singh, J. Upadhyaya, R.P. Bhullar, and P. Chelikani The third intracellular loop plays a critical role in bitter taste receptor activation Biochim Biophys Acta 1838 2014 231 236
100. S.P. Pydi, T. Sobotkiewicz, R. Billakanti, R.P. Bhullar, M.C. Loewen, and P. Chelikani Amino acid derivatives as bitter taste receptor (T2R) blockers J Biol Chem 289 2014 25054 25066
101. C. Reichling, W. Meyerhof, and M. Behrens Functions of human bitter taste receptors depend on N-glycosylation J Neurochem 106 2008 1138 1148
102. A. Rivero-Muller, K.C. Jonas, A.C. Hanyaloglu, and I. Huhtaniemi Di/oligomerization of GPCRs - mechanisms and functional significance Prog Mol Biol Transl Sci 117 2013 163 185
103. K.S. Robinett, D.A. Deshpande, M.M. Malone, and S.B. Liggett Agonist-promoted homologous desensitization of human airway smooth muscle bitter taste receptors Am J Respir Cell Mol Biol 45 2011 1069 1074
104. W.S. Roland, R.J. Gouka, H. Gruppen, M. Driesse, L. van Buren, G. Smit, and J.P. Vincken 6-Methoxyflavanones as bitter taste receptor blockers for hTAS2R39 PLoS One 9 2014 e94451
105. S. Rosenzweig, W. Yan, M. Dasso, and A.I. Spielman Possible novel mechanism for bitter taste mediated through cGMP J Neurophysiol 81 1999 1661 1665
106. N. Roudnitzky, B. Bufe, S. Thalmann, C. Kuhn, H.C. Gunn, C. Xing, B.P. Crider, M. Behrens, W. Meyerhof, and S.P. Wooding Genomic, genetic and functional dissection of bitter taste responses to artificial sweeteners Hum Mol Genet 20 2011 3437 3449
107. L. Ruiz-Avila, S.K. McLaughlin, D. Wildman, P.J. McKinnon, A. Robichon, N. Spickofsky, and R.F. Margolskee Coupling of bitter receptor to phosphodiesterase through transducin in taste receptor cells Nature 376 1995 80 85
108. L. Ruiz-Avila, D. Ming, and R.F. Margolskee An in vitro assay useful to determine the potency of several bitter compounds Chem Senses 25 2000 361 368
109. L. Ruiz-Avila, G.T. Wong, S. Damak, and R.F. Margolskee Dominant loss of responsiveness to sweet and bitter compounds caused by a single mutation in alpha-gustducin Proc Natl Acad Sci U S A 98 2001 8868 8873
110. E. Sainz, M.M. Cavenagh, J. Gutierrez, J.F. Battey, J.K. Northup, and S.L. Sullivan Functional characterization of human bitter taste receptors Biochem J 403 2007 537 543
111. T. Sakurai, T. Misaka, M. Ishiguro, K. Masuda, T. Sugawara, K. Ito, T. Kobayashi, S. Matsuo, Y. Ishimaru, T. Asakura, and K. Abe Characterization of the beta-d-glucopyranoside binding site of the human bitter taste receptor hTAS2R16 J Biol Chem 285 2010 28373 28378
112. C.J. Saunders, M. Christensen, T.E. Finger, and M. Tizzano Cholinergic neurotransmission links solitary chemosensory cells to nasal inflammation Proc Natl Acad Sci U S A 111 2014 6075 6080
113. H. Sekine, K. Takao, K. Yoshinaga, S. Kokubun, and M. Ikeda Effects of zinc deficiency and supplementation on gene expression of bitter taste receptors (TAS2Rs) on the tongue in rats Laryngoscope 122 2012 2411 2417
114. A.S. Shah, Y. Ben-Shahar, T.O. Moninger, J.N. Kline, and M.J. Welsh Motile cilia of human airway epithelia are chemosensory Science 325 2009 1131 1134
115. L.L. Silhan, K.S. Robinett, D.A. Deshpande, and S.B. Liggett Upregulation of bitter taste receptor cell surface expression by chronic agonist: a novel trafficking outcome that may minimize tachyphylaxis d73. Receptor input of airway networking 185 2012 American Thoracic Society A6271
116. J.P. Slack, A. Brockhoff, C. Batram, S. Menzel, C. Sonnabend, S. Born, M.M. Galindo, S. Kohl, S. Thalmann, L. Ostopovici-Halip, C.T. Simons, I. Ungureanu, K. Duineveld, C.G. Bologa, M. Behrens, S. Furrer, T.I. Oprea, and W. Meyerhof Modulation of bitter taste perception by a small molecule hTAS2R antagonist Curr Biol 20 2010 1104 1109
117. S. Soares, S. Kohl, S. Thalmann, N. Mateus, W. Meyerhof, and V. De Freitas Different phenolic compounds activate distinct human bitter taste receptors J Agric Food Chem 61 2013 1525 1533
118. J. Tan, R. Abrol, B. Trzaskowski, and W.A. Goddard III 3D structure prediction of TAS2R38 bitter receptors bound to agonists phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) J Chem Inf Model 52 2012 1875 1885
119. X. Tan, and M.J. Sanderson Bitter tasting compounds dilate airways by inhibiting airway smooth muscle calcium oscillations and calcium sensitivity Br J Pharmacol 171 2014 646 662
120. Y.X. Tao Constitutive activation of G protein-coupled receptors and diseases: insights into mechanisms of activation and therapeutics Pharmacol Ther 120 2008 129 148
121. S. Terrillon, C. Barberis, and M. Bouvier Heterodimerization of V1a and V2 vasopressin receptors determines the interaction with beta-arrestin and their trafficking patterns Proc Natl Acad Sci U S A 101 2004 1548 1553
122. S. Terrillon, and M. Bouvier Roles of G-protein-coupled receptor dimerization EMBO Rep 5 2004 30 34
123. S. Thalmann, M. Behrens, and W. Meyerhof Major haplotypes of the human bitter taste receptor TAS2R41 encode functional receptors for chloramphenicol Biochem Biophys Res Commun 435 2013 267 273
124. M. Tizzano, B.D. Gulbransen, A. Vandenbeuch, T.R. Clapp, J.P. Herman, H.M. Sibhatu, M.E. Churchill, W.L. Silver, S.C. Kinnamon, and T.E. Finger Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals Proc Natl Acad Sci U S A 107 2010 3210 3215
125. J. Upadhyaya, S.P. Pydi, N. Singh, R.E. Aluko, and P. Chelikani Bitter taste receptor T2R1 is activated by dipeptides and tripeptides Biochem Biophys Res Commun 398 2010 331 335
126. J.D. Upadhyaya, N. Singh, A.S. Sikarwar, R. Chakraborty, S.P. Pydi, R.P. Bhullar, S. Dakshinamurti, and P. Chelikani Dextromethorphan mediated bitter taste receptor activation in the pulmonary circuit causes vasoconstriction PLoS One 9 2014 e110373
127. M. Waldhoer, J. Fong, R.M. Jones, M.M. Lunzer, S.K. Sharma, E. Kostenis, P.S. Portoghese, and J.L. Whistler A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers Proc Natl Acad Sci U S A 102 2005 9050 9055
128. A. Wiener, M. Shudler, A. Levit, and M.Y. Niv BitterDB: a database of bitter compounds Nucleic Acids Res 40 2012 D413 D419
129. G.T. Wong, K.S. Gannon, and R.F. Margolskee Transduction of bitter and sweet taste by gustducin Nature 381 1996 796 800
130. W. Yan, G. Sunavala, S. Rosenzweig, M. Dasso, J.G. Brand, and A.I. Spielman 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 2001 C742 C751
131. C.H. Zhang, C. Chen, L.M. Lifshitz, K.E. Fogarty, M.S. Zhu, and R. Zhuge Activation of BK channels may not be required for bitter tastant-induced bronchodilation Nat Med 18 2012 648 650
132. Y. Zhang, M.A. Hoon, J. Chandrashekar, K.L. Mueller, B. Cook, D. Wu, C.S. Zuker, and N.J. Ryba Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways Cell 112 2003 293 301
133. C.H. Zhang, L.M. Lifshitz, K.F. Uy, M. Ikebe, K.E. Fogarty, and R. Zhuge The cellular and molecular basis of bitter tastant-induced bronchodilation PLoS Biol 11 2013 e1001501
134. T. Zhang, X.J. Luo, W.B. Sai, M.F. Yu, W.E. Li, Y.F. Ma, W. Chen, K. Zhai, G. Qin, D. Guo, Y.M. Zheng, Y.X. Wang, J.H. Shen, G. Ji, and Q.H. Liu Non-selective cation channels mediate chloroquine-induced relaxation in precontracted mouse airway smooth muscle PLoS One 9 2014 e101578