Taste 2 receptors or Bitter taste receptors (TAS2Rs) are G protein-coupled receptors expressed in oral sensory cells and a variety of non-gustatory tissues. The ~25 human TAS2Rs share low amino acid sequence identities with other GPCR families and are classified as broadly tuned "generalist" receptors with numerous, chemically diverse bitter agonists, as narrowly tuned "specialist" receptors with very few activators, as intermediately tuned receptors with an average number of agonists, or receptors specialized to interact with chemically defined activators [31]. The number of functional bitter taste receptor genes varies among species and orthologues might not be functionally conserved. Due to their expression in various tissues, the signal transduction of TAS2Rs is complex. Some TAS2Rs interact with drugs such as analgesic, anti-inflammatory, and antibacterial compounds. The specialist database BitterDB contains additional information on bitter compounds and receptors [13].

* Key recommended reading is highlighted with an asterisk

* Palmer RK. (2019) A Pharmacological Perspective on the Study of Taste. Pharmacol Rev, 71 (1): 20-48. [PMID:30559245]

1. Behrens M, Blank K, Meyerhof W. (2017) Blends of Non-caloric Sweeteners Saccharin and Cyclamate Show Reduced Off-Taste due to TAS2R Bitter Receptor Inhibition. Cell Chem Biol, 24 (10): 1199-1204.e2. [PMID:28919036]

2. 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 (21): 9860-6. [PMID:19817411]

3. 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 (2): 479-85. [PMID:15178431]

4. Behrens M, Gu M, Fan S, Huang C, Meyerhof W. (2018) Bitter substances from plants used in traditional Chinese medicine exert biased activation of human bitter taste receptors. Chem Biol Drug Des, 91 (2): 422-433. [PMID:28834122]

5. Behrens M, Gunn HC, Ramos PC, Meyerhof W, Wooding SP. (2013) Genetic, functional, and phenotypic diversity in TAS2R38-mediated bitter taste perception. Chem Senses, 38 (6): 475-84. [PMID:23632915]

6. Behrens M, Redel U, Blank K, Meyerhof W. (2019) The human bitter taste receptor TAS2R7 facilitates the detection of bitter salts. Biochem Biophys Res Commun, 512 (4): 877-881. [PMID:30928101]

7. Born S, Levit A, Niv MY, Meyerhof W, Behrens M. (2013) The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands. J Neurosci, 33 (1): 201-13. [PMID:23283334]

8. 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 (15): 6236-43. [PMID:17595105]

9. Brockhoff A, Behrens M, Roudnitzky N, Appendino G, Avonto C, Meyerhof W. (2011) Receptor agonism and antagonism of dietary bitter compounds. J Neurosci, 31 (41): 14775-82. [PMID:21994393]

10. 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 (4): 322-7. [PMID:15723792]

11. 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 (3): 397-401. [PMID:12379855]

12. Cui M, Chen B, Xu K, Rigakou A, Diamantakos P, Melliou E, Logothetis DE, Magiatis P. (2021) Activation of specific bitter taste receptors by olive oil phenolics and secoiridoids. Sci Rep, 11 (1): 22340. [PMID:34785711]

13. Dagan-Wiener A, Di Pizio A, Nissim I, Bahia MS, Dubovski N, Margulis E, Niv MY. (2019) BitterDB: taste ligands and receptors database in 2019. Nucleic Acids Res, 47 (D1): D1179-D1185. [PMID:30357384]

14. Di Pizio A, Waterloo LAW, Brox R, Löber S, Weikert D, Behrens M, Gmeiner P, Niv MY. (2020) Rational design of agonists for bitter taste receptor TAS2R14: from modeling to bench and back. Cell Mol Life Sci, 77 (3): 531-542. [PMID:31236627]

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16. Fletcher JN, Kinghorn AD, Slack JP, McCluskey TS, Odley A, Jia Z. (2011) In vitro evaluation of flavonoids from Eriodictyon californicum for antagonist activity against the bitterness receptor hTAS2R31. J Agric Food Chem, 59 (24): 13117-21. [PMID:22059530]

17. Fotsing JR, Darmohusodo V, Patron AP, Ching BW, Brady T, Arellano M, Chen Q, Davis TJ, Liu H, Servant G et al.. (2020) Discovery and Development of S6821 and S7958 as Potent TAS2R8 Antagonists. J Med Chem, 63 (9): 4957-4977. [PMID:32330040]

18. Greene TA, Alarcon S, Thomas A, Berdougo E, Doranz BJ, Breslin PA, Rucker JB. (2011) Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin. PLoS One, 6 (5): e20123. [PMID:21629661]

19. Hellfritsch C, Brockhoff A, Stähler F, Meyerhof W, Hofmann T. (2012) Human psychometric and taste receptor responses to steviol glycosides. J Agric Food Chem, 60 (27): 6782-93. [PMID:22616809]

20. 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. Chemosensory Perception, 2: 118–132. DOI: 10.1007/s12078-009-9049-1

21. Jaggupilli A, Singh N, De Jesus VC, Gounni MS, Dhanaraj P, Chelikani P. (2019) Chemosensory bitter taste receptors (T2Rs) are activated by multiple antibiotics. FASEB J, 33 (1): 501-517. [PMID:30011231]

22. Jaggupilli A, Singh N, Jesus VC, Duan K, Chelikani P. (2018) Characterization of the Binding Sites for Bacterial Acyl Homoserine Lactones (AHLs) on Human Bitter Taste Receptors (T2Rs). ACS Infect Dis, 4 (7): 1146-1156. [PMID:29799189]

23. 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 (5610): 1221-5. [PMID:12595690]

24. Kohl S, Behrens M, Dunkel A, Hofmann T, Meyerhof W. (2013) Amino acids and peptides activate at least five members of the human bitter taste receptor family. J Agric Food Chem, 61 (1): 53-60. [PMID:23214402]

25. 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 (45): 10260-5. [PMID:15537898]

26. Lang R, Lang T, Dunkel A, Ziegler F, Behrens M. (2022) Overlapping activation pattern of bitter taste receptors affect sensory adaptation and food perception. Front Nutr, 9: 1082698. [PMID:36601079]

27. Lang T, Frank O, Lang R, Hofmann T, Behrens M. (2022) Activation Spectra of Human Bitter Taste Receptors Stimulated with Cyclolinopeptides Corresponding to Fresh and Aged Linseed Oil. J Agric Food Chem, 70 (14): 4382-4390. [PMID:35364812]

28. Lang T, Lang R, Di Pizio A, Mittermeier VK, Schlagbauer V, Hofmann T, Behrens M. (2020) Numerous Compounds Orchestrate Coffee's Bitterness. J Agric Food Chem, 68 (24): 6692-6700. [PMID:32437139]

29. Levit A, Nowak S, Peters M, Wiener A, Meyerhof W, Behrens M, Niv MY. (2014) The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14. FASEB J, 28 (3): 1181-97. [PMID:24285091]

30. Mancuso G, Borgonovo G, Scaglioni L, Bassoli A. (2015) Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception. Molecules, 20 (10): 18907-22. [PMID:26501253]

31. 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 (2): 157-70. [PMID:20022913]

32. Morini G, Winnig M, Vennegeerts T, Borgonovo G, Bassoli A. (2021) Vanillin Activates Human Bitter Taste Receptors TAS2R14, TAS2R20, and TAS2R39. Front Nutr, 8: 683627. [PMID:34307435]

33. Narukawa M, Noga C, Ueno Y, Sato T, Misaka T, Watanabe T. (2011) Evaluation of the bitterness of green tea catechins by a cell-based assay with the human bitter taste receptor hTAS2R39. Biochem Biophys Res Commun, 405 (4): 620-5. [PMID:21272567]

34. Nowak S, Di Pizio A, Levit A, Niv MY, Meyerhof W, Behrens M. (2018) Reengineering the ligand sensitivity of the broadly tuned human bitter taste receptor TAS2R14. Biochim Biophys Acta Gen Subj, 1862 (10): 2162-2173. [PMID:30009876]

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36. Pydi SP, Jaggupilli A, Nelson KM, Abrams SR, Bhullar RP, Loewen MC, Chelikani P. (2015) Abscisic Acid Acts as a Blocker of the Bitter Taste G Protein-Coupled Receptor T2R4. Biochemistry, 54 (16): 2622-31. [PMID:25844797]

37. Roland WS, Gouka RJ, Gruppen H, Driesse M, van Buren L, Smit G, Vincken JP. (2014) 6-methoxyflavanones as bitter taste receptor blockers for hTAS2R39. PLoS One, 9 (4): e94451. [PMID:24722342]

38. Roland WS, van Buren L, Gruppen H, Driesse M, Gouka RJ, Smit G, Vincken JP. (2013) Bitter taste receptor activation by flavonoids and isoflavonoids: modeled structural requirements for activation of hTAS2R14 and hTAS2R39. J Agric Food Chem, 61 (44): 10454-66. [PMID:24117141]

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40. Roudnitzky N, Behrens M, Engel A, Kohl S, Thalmann S, Hübner S, Lossow K, Wooding SP, Meyerhof W. (2015) Receptor Polymorphism and Genomic Structure Interact to Shape Bitter Taste Perception. PLoS Genet, 11 (9): e1005530. [PMID:26406243]

41. Sakurai T, Misaka T, Ueno Y, Ishiguro M, Matsuo S, Ishimaru Y, Asakura T, Abe K. (2010) The human bitter taste receptor, hTAS2R16, discriminates slight differences in the configuration of disaccharides. Biochem Biophys Res Commun, 402 (4): 595-601. [PMID:20965151]

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44. Soares S, Silva MS, García-Estevez I, Groβmann P, Brás N, Brandão E, Mateus N, de Freitas V, Behrens M, Meyerhof W. (2018) Human Bitter Taste Receptors Are Activated by Different Classes of Polyphenols. J Agric Food Chem, 66 (33): 8814-8823. [PMID:30056706]

45. Suess B, Brockhoff A, Meyerhof W, Hofmann T. (2018) The Odorant ( R)-Citronellal Attenuates Caffeine Bitterness by Inhibiting the Bitter Receptors TAS2R43 and TAS2R46. J Agric Food Chem, 66 (10): 2301-2311. [PMID:27569025]

46. Thalmann S, Behrens M, Meyerhof W. (2013) Major haplotypes of the human bitter taste receptor TAS2R41 encode functional receptors for chloramphenicol. Biochem Biophys Res Commun, 435 (2): 267-73. [PMID:23632330]

47. Thomas A, Sulli C, Davidson E, Berdougo E, Phillips M, Puffer BA, Paes C, Doranz BJ, Rucker JB. (2017) The Bitter Taste Receptor TAS2R16 Achieves High Specificity and Accommodates Diverse Glycoside Ligands by using a Two-faced Binding Pocket. Sci Rep, 7 (1): 7753. [PMID:28798468]

48. Upadhyaya J, Pydi SP, Singh N, Aluko RE, Chelikani P. (2010) Bitter taste receptor T2R1 is activated by dipeptides and tripeptides. Biochem Biophys Res Commun, 398 (2): 331-5. [PMID:20599705]

49. Wang Y, Zajac AL, Lei W, Christensen CM, Margolskee RF, Bouysset C, Golebiowski J, Zhao H, Fiorucci S, Jiang P. (2019) Metal Ions Activate the Human Taste Receptor TAS2R7. Chem Senses, 44 (5): 339-347. [PMID:31066447]

50. Wooding S, Gunn H, Ramos P, Thalmann S, Xing C, Meyerhof W. (2010) Genetics and bitter taste responses to goitrin, a plant toxin found in vegetables. Chem Senses, 35 (8): 685-92. [PMID:20551074]

51. Yamazaki T, Sagisaka M, Ikeda R, Nakamura T, Matsuda N, Ishii T, Nakayama T, Watanabe T. (2014) The human bitter taste receptor hTAS2R39 is the primary receptor for the bitterness of theaflavins. Biosci Biotechnol Biochem, 78 (10): 1753-6. [PMID:25273142]

Maik Behrens Leibniz Institute for Food Systems Biology at the Technical University of Munich Lise-Meitner-Str. 34 85354 Freising Germany