Clinical Role of Extraoral Bitter Taste Receptors
Abstract
:1. Introduction
2. TAS2R Bitter Taste Receptor Activation and Intracellular Signalling Cascades
3. The Role of Bitter Taste Receptors in Rhinosinusitis
4. TAS2R Receptors in Lower Airways
5. Bitter Taste Receptors in Other Systems and Diseases
6. The Role of TAS2R Receptors in Eating Behaviours, Obesity and Diabetes
7. TAS2Rs’ Impact on Longevity
8. TAS2Rs in Cancer
9. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
GPCRs | G protein-coupled receptors |
PTC | Phenylthiocarbamide |
GI | Gastrointestinal |
PYY | Peptide YY |
GIP | Gastric inhibitory peptide |
GLP-1 | Glucagon-like peptide-1 |
PGD2 | Prostaglandin D2 |
EEC | Enteroendocrine cells |
CCK | Cholecystokinin |
ASM | Airway smooth muscle |
PASM | Pulmonary artery smooth muscle |
LMs | Lung macrophages |
CBMCs | Cord blood-derived mast cells |
MSC | Mesenchymal stromal cells |
VSMC | Vascular smooth muscle cell |
WBC | White blood cells |
PDE | Phosphodiesterase |
cNMP | Cyclic nucleotide-inhibited channels |
PLCβ2 | Phospholipase C isoform β2 |
IP3 | Inositol trisphosphate |
IP3RIII | IP3 receptor type III |
TRP | Transient receptor potential proteins |
TRPM5 | Transient receptor protein M5 |
CRS | Chronic rhinosinusitis |
CRSwNP | Chronic rhinosinusitis with nasal polyps |
CRSsNP | Chronic rhinosinusitis without nasal polyps |
NO | Nitric oxide |
NOS | Nitric oxide synthase |
AHLs | Acyl-homoserine lactones |
C4HSL | N-butyryl-L-homoserine lactone |
C12HSL | N-3-oxo-dodecanoyl-L-homoserine lactone |
Ca2+ | Calcium ion |
K+ | Potassium ion |
SNPs | Single nucleotide polymorphisms |
FESS | Functional endoscopic sinus surgery |
QoL | Quality of life |
CT | Computer tomography |
CF | Cystic fibrosis |
VDCCs | Voltage-dependent calcium channels |
COPD | Chronic obstructive pulmonary disease |
HPKs | Human primary keratinocytes |
SCCs | Solitary chemosensory cells |
BMI | Body mass index |
DB | Denatonium benzoate |
ABCB1 | ATP-binding cassette B1 |
GAS | Gastric acid secretion |
AHL-12 | N-acetyl-dodecanoyl homoserine |
PTU | Phenylthiourea |
References
- Drayna, D. Human Taste Genetics. Annu. Rev. Genomics Hum. Genet. 2005, 6, 217–235. [Google Scholar] [CrossRef]
- Bachmanov, A.; Bosak, N.; Lin, C.; Matsumoto, I.; Ohmoto, M.; Reed, D.R.; Nelson, T.M. Genetics of Taste Receptors. Curr. Pharm. Des. 2014, 20, 2669–2683. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kikut-Ligaj, D.; Trzcielinska-Lorych, J. How taste works: Cells, receptors and gustatory perception. Cell. Mol. Biol. Lett. 2015, 20, 699–716. [Google Scholar] [CrossRef] [PubMed]
- Lee, H.; Macpherson, L.J.; Parada, C.A.; Zuker, C.S.; Ryba, N.J.P. Rewiring the taste system. Nature 2017, 548, 330–333. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Challis, R.C.; Ma, M. Sour taste finds closure in a potassium channel. Proc. Natl. Acad. Sci. USA 2016, 113, 246–247. [Google Scholar] [CrossRef] [Green Version]
- Bushman, J.D.; Ye, W.; Liman, E.R. A proton current associated with sour taste: Distribution and functional properties. FASEB J. 2015, 29, 3014–3026. [Google Scholar] [CrossRef] [Green Version]
- Carey, R.M.; Adappa, N.D.; Palmer, J.N.; Lee, R.J.; Cohen, N.A. Taste Receptors: Regulators of Sinonasal Innate Immunity. Laryngoscope Investig. Otolaryngol. 2016, 1, 88–95. [Google Scholar] [CrossRef]
- Fox, A.L. Taste blindness. Science 1931, 73, 14. [Google Scholar]
- Adler, E.; Hoon, M.A.; Mueller, K.L.; Chandrashekar, J.; Ryba, N.J.; Zuker, C.S. A novel family of mammalian taste receptors. Cell 2000, 100, 693–702.Behrens, M.; Meyerhof, W. Oral and extraoral bitter taste receptors. Results Probl. Cell Differ. 2010, 52, 87–99. [Google Scholar]
- Behrens, M.; Meyerhof, W. Oral and extraoral bitter taste receptors. Results Probl. Cell Differ. 2010, 52, 87–99. [Google Scholar]
- Avau, B.; Depoortere, I. The bitter truth about bitter taste receptors: Beyond sensing bitter in the oral cavity. Acta Physiol. 2016, 216, 407–420. [Google Scholar] [CrossRef] [PubMed]
- Shaik, F.A.; Singh, N.; Arakawa, M.; Duan, K.; Bhullar, R.P.; Chelikani, P. Bitter taste receptors: Extraoral roles in pathophysiology. Int. J. Biochem. Cell. Biol. 2016, 77, 197–204. [Google Scholar] [CrossRef] [PubMed]
- Mennella, J.A.; Pepino, M.Y.; Reed, D.R. Genetic and environmental determinants of bitter perception and sweet preferences. Pediatrics 2005, 115, e216–e222. [Google Scholar] [CrossRef] [Green Version]
- Rozengurt, N.; Wu, S.; Chen, M.C.; Huang, C.; Sternini, C.; Rozengurt, E. Co-localization of the {alpha} subunit of gustducin with PYY and GLP-1 in L cells of human colon. Am. J. Physiol. Gastrointest. Liver Physiol. 2006, 291, G792–G802. [Google Scholar] [CrossRef]
- Shah, A.S.; Ben-Shahar, Y.; Moninger, T.O.; Kline, J.N.; Welsh, M.J. Motile cilia of human airway epithelia are chemosensory. Science 2009, 325, 1131–1134. [Google Scholar] [CrossRef] [Green Version]
- Deshpande, D.A.; Wang, W.C.; McIlmoyle, E.L.; Robinett, K.S.; Schillinger, R.M.; An, S.S.; Sham, J.S.K.; Liggett, S.B. Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nat. Med. 2010, 16, 1299–1304. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Le Neve, B.; Foltz, M.; Daniel, H.; Gouka, R. The steroid glycoside H.g.-12 from Hoodia gordonii activates the human bitter receptor TAS2R14 and induces CCK release from HuTu-80 cells. Am. J. Physiol. Gastrointest. Liver Physiol. 2010, 299, G1368–G1375. [Google Scholar] [CrossRef] [PubMed]
- Jeon, T.I.; Seo, Y.K.; Osborne, T.F. Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving CCK. Biochem, J. 2011, 438, 33–37. [Google Scholar] [CrossRef]
- Lee, R.J.; Xiong, G.; Kofonow, J.M.; Chen, B.; Lysenko, A.; Jiang, P.; Abraham, V.; Doghramji, L.; Adappa, N.D.; Palmer, J.N.; et al. T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection. J. Clin. Invest. 2012, 122, 4145–4159. [Google Scholar] [CrossRef] [Green Version]
- Grassin-Delyle, S.; Abrial, C.; Fayad-Kobeissi, S.; Brollo, M.; Faisy, C.; Alvarez, J.C.; Naline, E.; Devillier, P. The expression and relaxant effect of bitter taste receptors in human bronchi. Respir. Res. 2013, 14, 134. [Google Scholar] [CrossRef] [Green Version]
- Orsmark-Pietras, C.; James, A.; Konradsen, J.R.; Nordlund, B.; Soderhall, C.; Pulkkinen, V.; Pedroletti, C.; Daham, K.; Kupczyk, M.; Dahlén, B.; et al. Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics. Eur. Respir. J. 2013, 42, 65–78. [Google Scholar] [CrossRef] [Green Version]
- Foster, S.R.; Porrello, E.R.; Purdue, B.; Chan, H.W.; Voigt, A.; Frenzel, S.; Hannan, R.D.; Moritz, K.M.; Simmons, D.G.; Molenaar, P.; et al. Expression, Regulation and Putative Nutrient-Sensing Function of Taste GPCRs in the Heart. PLoS ONE 2013, 8, e64579. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lund, T.C.; Kobs, A.J.; Kramer, A.; Nyquist, M.; Kuroki, M.T.; Osborn, J.; Lidke, D.S.; Low-Nam, S.T.; Blazar, B.R.; Tolar, J. Bone Marrow Stromal and Vascular Smooth Muscle Cells Have Chemosensory Capacity via Bitter Taste Receptor Expression. PLoS ONE 2013, 8, e58945. [Google Scholar] [CrossRef] [Green Version]
- Singh, N.; Chakraborty, R.; Bhullar, R.P.; Chelikani, P. Differential expression of bitter taste receptors in non-cancerous breast epithelial and breast cancer cells. Biochem. Biophys. Res. Commun. 2014, 446, 499–503. [Google Scholar] [CrossRef]
- Ekoff, M.; Choi, J.H.; James, A.; Dahlen, B.; Nilsson, G.; Dahlen, S.E. Bitter taste receptor (TAS2R) agonists inhibit IgE-dependent mast cell activation. J. Allergy Clin. Immunol. 2014, 134, 475–478. [Google Scholar] [CrossRef]
- Clark, A.A.; Dotson, C.D.; Elson, A.E.T.; Voigt, A.; Boehm, U.; Meyerhof, W.; Steinle, N.I.; Munger, S.D. TAS2R bitter taste receptors regulate thyroid function. FASEB J. 2015, 29, 164–172. [Google Scholar] [CrossRef] [Green Version]
- Yu, Y.; Hao, G.; Zhang, Q.; Hua, W.; Wang, M.; Zhou, W.; Zong, S.; Huang, M.; Wen, X. Berberine induces GLP-1 secretion through activation of bitter taste receptor pathways. Biochem. Pharmacol. 2015, 97, 173–177. [Google Scholar] [CrossRef]
- Wölfle, U.; Elsholz, F.A.; Kersten, A.; Haarhaus, B.; Müller, W.E.; Schempp, C.M. Expression and functional activity of the bitter taste receptors TAS2R1 and TAS2R38 in human keratinocytes. Skin Pharmacol. Physiol. 2015, 28, 137–146. [Google Scholar] [CrossRef] [PubMed]
- Wölfle, U.; Elsholz, F.A.; Kersten, A.; Haarhaus, B.; Schumacher, U.; Schempp, C.M. Expression and functional activity of the human bitter taste receptor TAS2R38 in human placental tissues and JEG-3 cells. Molecules 2016, 21, 306. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jaggupilli, A.; Singh, N.; Upadhyaya, J.; Sikarwar, A.S.; Arakawa, M.; Dakshinamurti, S.; Bhullar, R.P.; Duan, K.; Chelikani, P. Analysis of the expression of human bitter taste receptors in extraoral tissues. Mol. Cell. Biochem. 2017, 426, 137–147. [Google Scholar] [CrossRef] [PubMed]
- Latorre, R.; Huynh, J.; Mazzoni, M.; Gupta, A.; Bonora, E.; Clavenzani, P.; Chang, L.; Mayer, E.A.; De Giorgio, R.; Sternini, C. Expression of the Bitter Taste Receptor, T2R38, in Enteroendocrine Cells of the Colonic Mucosa of Overweight/Obese vs. Lean Subjects. PLoS ONE 2016, 11, e0147468. [Google Scholar] [CrossRef]
- Zheng, K.; Lu, P.; Delpapa, E.; Bellve, K.; Deng, R.; Condon, J.C.; Fogarty, K.; Lifshitz, L.M.; Simas, T.M.; Shi, F.; et al. Bitter taste receptors as targets for tocolytics in preterm labor therapy. FASEB J. 2017, 31, 4037–4052. [Google Scholar] [CrossRef] [Green Version]
- Hariri, B.M.; McMahon, D.B.; Chen, B.; Freund, J.R.; Mansfield, C.J.; Doghramji, L.J.; Adappa, N.D.; Palmer, J.N.; Kennedy, D.W.; Reed, D.R.; et al. Flavones modulate respiratory epithelial innate immunity: Anti-inflammatory effects and activation of the T2R14 receptor. J. Biol. Chem. 2017, 292, 8484–8497. [Google Scholar] [CrossRef] [Green Version]
- Freund, J.R.; Mansfield, C.J.; Doghramji, L.J.; Adappa, N.D.; Palmer, J.N.; Kennedy, D.W.; Reed, D.R.; Jiang, P.; Lee, R.J. Activation of airway epithelial bitter taste receptors by Pseudomonas aeruginosa quinolones modulates calcium, cyclic-AMP, and nitric oxide signaling. J. Biol. Chem. 2018, 293, 9824–9840. [Google Scholar] [CrossRef] [Green Version]
- Shaw, L.; Mansfield, C.; Colquitt, L.; Lin, C.; Ferreira, J.; Emmetsberger, J.; Reed, D.R. Personalized expression of bitter ‘taste’ receptors in human skin. PLoS ONE 2018, 13, e0205322. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Grassin-Delyle, S.; Salvator, H.; Mantov, N.; Abrial, C.; Brollo, M.; Faisy, C.; Naline, E.; Couderc, L.J.; Devillier, P. Bitter Taste Receptors (TAS2Rs) in Human Lung Macrophages: Receptor Expression and Inhibitory Effects of TAS2R Agonists. Front. Physiol. 2019, 10, 1–13. [Google Scholar] [CrossRef]
- Cont, G.; Paviotti, G.; Montico, M.; Paganin, P.; Guerra, M.; Trappan, A.; Demarini, S.; Gasparini, P.; Robino, A. TAS2R38 bitter taste genotype is associated with complementary feeding behavior in infants. Genes Nutr. 2019, 14, 1–7. [Google Scholar] [CrossRef]
- Governini, L.; Semplici, B.; Pavone, V.; Crifasi, L.; Marrocco, C.; De Leo, V.; Arlt, E.; Gudermann, T.; Boekhoff, I.; Luddiet, A.; et al. Expression of Taste Receptor 2 Subtypes in Human Testis and Sperm. J. Clin. Med. 2020, 9, 264. [Google Scholar] [CrossRef] [Green Version]
- McLaughlin, S.; McKinnon, P.; Margolskee, R. Gustducin is a taste-cell-specific G protein closely related to the transducins. Nature 1992, 357, 563–569. [Google Scholar] [CrossRef]
- Wong, G.; Gannon, K.; Margolskee, R. Transduction of bitter and sweet taste by gustducin. Nature 1996, 381, 796–800. [Google Scholar] [CrossRef]
- Huang, L.; Shanker, Y.; Dbuauskaite, J.; Zheng, J.; Yan, W.; Rosenzweig, S.; Spielman, A.I.; Max, M.; Margolskee, R.F. Gg13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium. Nat. Neurosci. 1999, 2, 1055–1062. [Google Scholar] [CrossRef]
- Margolskee, R.F. Molecular mechanisms of bitter and sweet taste transduction. J. Biol. Chem. 2002, 277, 1–4. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Romanov, R.A.; Rogachevskaja, O.A.; Bystrova, M.F.; Jiang, P.; Margolskee, R.F.; Kolesnikov, S.S. Afferent neurotransmission mediated by hemichannels in mammalian taste cells. EMBO J. 2007, 26, 657–667. [Google Scholar] [CrossRef] [PubMed]
- Liu, D.; Liman, E.R. Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proc. Natl. Acad. Sci. USA 2003, 100, 15160–15165. [Google Scholar] [CrossRef] [Green Version]
- Prawitt, D.; Monteilh-Zoller, M.K.; Brixel, L.; Spangenberg, C.; Zabel, B.; Fleig, A.; Penner, R. TRPM5 is a transient Ca2+ activated cation channel responding to rapid changes in [Ca2+]i. Proc. Natl. Acad. Sci. USA 2003, 100, 15166–15171. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ullrich, N.D.; Voetsa, T.; Prenena, J.; Vennekensa, R.; Talaveraa, K.; Droogmansa, G.; Nilius, B. Comparison of functional proper-ties of the Ca2+-activated cation channels TRPM4 and TRPM5 from mice. Cell Calcium 2005, 37, 267–278. [Google Scholar] [CrossRef]
- Zhang, Y.; Hoon, M.A.; Chandrashekar, J.; Mueller, K.L.; Cook, B.; Wu, D.; Zuker, C.S.; Ryba, N.J. Coding of sweet, bitter, and umami tastes: Different receptor cells sharing similar signaling pathways. Cell 2003, 112, 293–301. [Google Scholar] [CrossRef] [Green Version]
- Glendinning, J.I. Is the bitter rejection response always adaptive? Physiol. Behav. 1994, 56, 1217–1227. [Google Scholar] [CrossRef]
- Meyerhof, W.; Batram, C.; Kuhn, C.; Brockhoff, A.; Chudoba, E.; Bufe, B.; Appendino, G.; Behrens, M. The molecular receptive ranges of human TAS2R bitter taste receptors. Chem. Senses 2010, 35, 157–170. [Google Scholar] [CrossRef]
- Behrens, M.; Brockhoff, A.; Kuhn, C.; Bufe, B.; Winnig, M.; Meyerhof, W. The human taste receptor hTAS2R14 responds to a variety of different bitter compounds. Biochem. Biophys. Res. Commun. 2004, 319, 479–485. [Google Scholar] [CrossRef]
- Brockhoff, A.; Behrens, M.; Massarotti, A.; Appendino, G.; Meyerhof, W. Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium. J. Agric. Food Chem. 2007, 55, 6236–6243. [Google Scholar] [CrossRef]
- Sainz, E.; Cavenagh, M.M.; Gutierrez, J.; Battey, J.F.; Northup, J.K.; Sullivan, S.L. Functional characterization of human bitter taste receptors. Biochem. J. 2007, 403, 537–543. [Google Scholar] [CrossRef]
- Kim, U.K.; Drayna, D. Genetics of individual differences in bitter taste perception: Lessons from the PTC gene. Clin. Genet. 2005, 67, 275–280. [Google Scholar] [CrossRef]
- Meyerhof, W. Elucidation of mammalian bitter taste. Rev. Physiol. Biochem. Pharmacol. 2005, 154, 37–72. [Google Scholar]
- Kim, U.; Wooding, S.; Ricci, D.; Jorde, L.B.; Drayna, D. Worldwide haplotype diversity and coding sequence variation at human bitter taste receptor loci. Hum. Mutat. 2005, 26, 199–204. [Google Scholar] [CrossRef]
- Hastan, D.; Fokkens, W.J.; Bachert, C.; Newson, R.B.; Bislimovska, J.; Bockelbrink, A.; Bousquet, P.J.; Brozek, G.; Bruno, A.; Dahlén, S.E.; et al. Chronic rhinosinusitis in Europe—An underestimated disease. A GA(2)LEN study. Allergy 2011, 66, 1216–1223. [Google Scholar] [CrossRef] [PubMed]
- Pleis, J.R.; Lucas, J.W.; Ward, B.W. Summary Health Statistics for U.S. Adults: National Health Interview Survey. Vital Health Stat. 2009, 2008, 1–157. [Google Scholar]
- Fokkens, W.J.; Lund, V.J.; Mullol, J.; Bachert, C.; Alobid, I.; Baroody, F.; Cohen, N.; Cervin, A.; Douglas, R.; Gevaert, P.; et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol. Suppl. 2012, 23, 1–298. [Google Scholar]
- Carey, R.M.; Lee, R.J.; Cohen, N.A. Taste Receptors in Upper Airway Immunity. Adv. Otorhinolaryngol. 2016, 79, 91–102. [Google Scholar] [PubMed]
- Rowan, N.R.; Soler, Z.M.; Othieno, F.; Storck, K.A.; Smith, T.L.; Schlosser, R.J. Impact of bitter taste receptor phenotype upon clinical presentation in chronic rhinosinusitis. Int. Forum Allergy Rhinol. 2018, 8, 1013–1020. [Google Scholar] [CrossRef] [PubMed]
- Carey, R.M.; Workman, A.D.; Yan, C.H.; Chen, B.; Adappa, N.D.; Palmer, J.N.; Kennedy, D.W.; Lee, R.J.; Cohen, N.A. Sinonasal T2R-mediated nitric oxide production in response to Bacillus cereus. Am. J. Rhinol. Allergy 2017, 31, 211–215. [Google Scholar] [CrossRef] [Green Version]
- Yan, C.H.; Hahn, S.; McMahon, D.; Bonislawski, D.; Kennedy, D.W.; Adappa, N.D.; Palmer, J.N.; Jiang, P.; Lee, R.J.; Cohen, N.A. Nitric oxide production is stimulated by bitter taste receptors ubiquitously expressed in the sinonasal cavity. Am. J. Rhinol. Allergy. 2017, 31, 85–92. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jimenez, P.N.; Koch, G.; Thompson, J.A.; Xavier, K.B.; Cool, R.H.; Quax, W.J. The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. Microbiol. Mol. Biol. Rev. 2012, 76, 46–65. [Google Scholar] [CrossRef] [Green Version]
- Maurer, S.; Wabnitz, G.H.; Kahle, N.A.; Stegmaier, S.; Prior, B.; Giese, T.; Gaida, M.M.; Samstag, Y.; Hansch, G.M. Tasting Pseudomonas aeruginosa biofilms: Human neutrophils express the bitter receptor T2R38 as sensor for the quorum sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone. Front. Immunol. 2015, 6, 369. [Google Scholar] [CrossRef] [Green Version]
- Lee, R.J.; Hariri, B.M.; McMahon, D.B.; Chen, B.; Doghramji, L.; Adappa, N.D.; Palmer, J.N.; Kennedy, D.W.; Jiang, P.; Margolskee, R.F.; et al. Bacterial d-amino acids suppress sinonasal innate immunity through sweet taste receptors in solitary chemosensory cells. Sci. Signal. 2017, 10. [Google Scholar] [CrossRef] [Green Version]
- Mfuna Endam, L.; Filali-Mouhim, A.; Boisvert, P.; Boulet, L.P.; Bossé, Y.; Desrosiers, M. Genetic variations in taste receptors are associated with chronic rhinosinusitis: A replication study. Int. Forum Allergy Rhinol. 2014, 4, 200–206. [Google Scholar] [CrossRef]
- Deshaware, S.; Singhal, R. Genetic variation in bitter taste receptor gene TAS2R38, PROP taster status and their association with body mass index and food preferences in Indian population. Gene 2017, 627, 363–368. [Google Scholar] [CrossRef]
- Lee, R.J.; Cohen, N.A. The emerging role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis. Am. J. Rhinol. Allergy 2013, 27, 283–286. [Google Scholar] [CrossRef]
- Lee, R.J.; Cohen, N.A. Role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis. Curr. Opin. Allergy Clin. Immunol. 2015, 15, 14–20. [Google Scholar] [CrossRef] [Green Version]
- Adappa, N.D.; Howland, T.J.; Palmer, J.N.; Kennedy, D.W.; Doghramji, L.; Lysenko, A.; Reed, D.R.; Lee, R.J.; Cohen, N.A. Genetics of the taste receptor T2R38 correlates with chronic rhinosinusitis necessitating surgical intervention. Int. Forum Allergy Rhinol. 2013, 3, 184–187. [Google Scholar] [CrossRef]
- Adappa, N.D.; Zhang, Z.; Palmer, J.N.; Kennedy, D.W.; Doghramji, L.; Lysenko, A.; Reed, D.R.; Scott, T.; Zhao, N.W.; Owens, D.; et al. The bitter taste receptor T2R38 is an independent risk factor for chronic rhinosinusitis requiring sinus surgery. Int. Forum Allergy Rhinol. 2014, 4, 3–7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Adappa, N.D.; Farquhar, D.; Palmer, J.N.; Kennedy, D.W.; Doghramji, L.; Morris, S.A.; Owens, D.; Mansfield, C.; Lysenko, A.; Lee, R.J.; et al. TAS2R38 genotype predicts surgical outcome in nonpolypoid chronic rhinosinusitis. Int. Forum Allergy Rhinol. 2016, 6, 25–33. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dżaman, K.; Zagor, M.; Sarnowska, E.; Krzeski, A.; Kantor, I. The correlation of TAS2R38 gene variants with higher risk for chronic rhinosinusitis in Polish patients. Otolaryngol. Pol. 2016, 70, 13–18. [Google Scholar] [CrossRef]
- Cantone, E.; Negri, R.; Roscetto, E.; Grassia, R.; Catania, M.R.; Capasso, P.; Maffei, M.; Soriano, A.A.; Leone, C.A.; Iengo, M.; et al. In vivo Biofilm Formation, Gram-Negative Infections and TAS2R38 Polymorphisms in CRSw NP Patients. Laryngoscope 2018, 128, E339–E345. [Google Scholar] [CrossRef]
- Adappa, N.D.; Truesdale, C.M.; Workman, A.D.; Doghramji, L.; Mansfield, C.; Kennedy, D.W.; Palmer, J.N.; Cowart, B.J.; Cohen, N.A. Correlation of T2R38 taste phenotype and in vitro biofilm formation from nonpolypoid chronic rhinosinusitis patients. Int. Forum Allergy Rhinol. 2016, 6, 783–791. [Google Scholar] [CrossRef]
- Cohen, N.A. The genetics of the bitter taste receptor T2R38 in upper airway innate immunity and implications for chronic rhinosinusitis. Laryngoscope 2017, 127, 44–51. [Google Scholar] [CrossRef] [Green Version]
- Gallo, S.; Grossi, S.; Montrasio, G.; Binelli, G.; Cinquetti, R.; Simmen, D.; Castelnuovo, P.; Campomenosi, P. TAS2R38 taste receptor gene and chronic rhinosinusitis: New data from an Italian population. BMC Med. Genet. 2016, 17, 54. [Google Scholar] [CrossRef] [Green Version]
- Adappa, N.D.; Workman, A.D.; Hadjiliadis, D.; Dorgan, D.J.; Frame, D.; Brooks, S.; Doghramji, L.; Palmer, J.N.; Mansfield, C.; Reed, D.R.; et al. T2R38 genotype is correlated with sinonasal quality of life in homozygous ΔF508 cystic fibrosis patients. Int. Forum Allergy Rhinol. 2016, 6, 356–361. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Singla, V.; Reiter, J.F. The primary cilium as the cell’s antenna: Signaling at a sensory organelle. Science 2006, 313, 629–633. [Google Scholar] [CrossRef] [Green Version]
- Zhang, C.H.; Chen, C.; Lifshitz, L.M.; Fogarty, K.E.; Zhu, M.S.; ZhuGe, R. Activation of BK channels may not be required for bitter tastant-induced bronchodilation. Nat. Med. 2012, 18, 648–650. [Google Scholar] [CrossRef]
- Zhang, C.H.; Lifshitz, L.M.; Uy, K.F.; Ikebe, M.; Fogarty, K.E.; ZhuGe, R. The cellular and molecular basis of bitter tastant-induced bronchodilation. PLoS Biol. 2013, 11, e1001501. [Google Scholar] [CrossRef]
- Caramori, G.; Adcock, I. Pharmacology of airway inflammation in asthma and COPD. Pulm. Pharmacol. Ther. 2003, 16, 247–277. [Google Scholar] [CrossRef]
- Hershenson, M.B.; Brown, M.; Camoretti-Mercado, B.; Solway, J. Airway smooth muscle in asthma. Annu. Rev. Pathol. 2008, 3, 523–555. [Google Scholar] [CrossRef]
- Tliba, O.; Panettieri, R.A. Noncontractile functions of airway smooth muscle cells in asthma. Annu. Rev. Physiol. 2009, 71, 509–535. [Google Scholar] [CrossRef] [PubMed]
- Gopallawa, I.; Freund, J.R.; Lee, R.J. Bitter taste receptors stimulate phagocytosis in human macrophages through calcium, nitric oxide, and cyclic-GMP signaling. Cell Mol. Life Sci. 2020, 10, 1–16. [Google Scholar] [CrossRef]
- Robinett, K.S.; Koziol-White, C.J.; Akoluk, A.; An, S.S.; Panettieri, R.A., Jr.; Liggett, S.B. Bitter taste receptor function in asthmatic and nonasthmatic human airway smooth muscle cells. Am. J. Respir. Cell Mol. Biol. 2014, 50, 678–683. [Google Scholar] [CrossRef] [Green Version]
- Sharma, P.; Panebra, A.; Pera, T.; Tiegs, B.C.; Hershfeld, A.; Kenyon, L.C.; Deshpande, D.A. Anti-mitogenic effect of bitter taste receptor agonists on airway smooth muscle cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 2015, 310, L365–L376. [Google Scholar] [CrossRef] [Green Version]
- Brightling, C.E.; Bradding, P.; Symon, F.A.; Holgate, S.T.; Wardlaw, A.J.; Pavord, I.D. Mast-cell infiltration of airway smooth muscle in asthma. N. Engl. J. Med. 2002, 346, 1699–1705. [Google Scholar] [CrossRef]
- Belvisi, M.G.; Dale, N.; Birrell, M.A.; Canning, B.J. Bronchodilator activity of bitter tastants in human tissue. Nat. Med. 2011, 17, 776–778. [Google Scholar] [CrossRef]
- Morice, A.H.; Bennett, R.T.; Chaudhry, M.A.; Cowen, M.E.; Griffin, S.C.; Loubani, M. Effect of bitter tastants on human bronchi. Nat. Med. 2011, 17, 775. [Google Scholar] [CrossRef]
- Nayak, A.P.; Villalba, D.; Deshpande, D.A. Bitter Taste Receptors: An Answer to Comprehensive Asthma Control? Curr. Allergy Asthma Rep. 2019, 19, 48. [Google Scholar] [CrossRef] [PubMed]
- Nayak, A.P.; Shah, S.D.; Michael, J.V.; Deshpande, D.A. Bitter taste receptors for asthma therapeutics. Front. Physiol. 2019, 10, 884. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shiffman, D.; Ellis, S.G.; Rowland, C.M.; Malloy, M.J.; Luke, M.M.; Iakoubova, O.A.; Pullinger, C.R.; Cassano, J.; Aouizerat, B.E.; Fenwick, R.G.; et al. Identification of four gene variants associated with myocardial infarction. Am. J. Hum. Genet. 2005, 77, 596–605. [Google Scholar] [CrossRef] [Green Version]
- Shiffman, D.; O’Meara, E.S.; Bare, L.A.; Rowland, C.M.; Louie, J.Z.; Arellano, A.R.; Lumley, T.; Rice, K.; Iakoubova, O.; Luke, M.M.; et al. Association of gene variants with incident myocardial infarction in the cardiovascular health study. Arterioscler. Thromb. Vasc. Biol. 2008, 28, 173–179. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Garcia-Esparcia, P.; Schluter, A.; Carmona, M.; Moreno, J.; Ansoleaga, B.; Torrejon-Escribano, B.; Gustincich, S.; Pujol, A.; Ferrer, I. Functional genomics reveals dysregulation of cortical olfactory receptors in Parkinson disease: Novel putative chemoreceptors in the human brain. J. Neuropathol. Exp. Neurol. 2013, 72, 524–539. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ansoleaga, B.; Garcia-Esparcia, P.; Pinacho, R.; Haro, J.M.; Ramos, B.; Ferrer, I. Decrease in olfactory and taste receptor expression in the dorsolateral prefrontal cortex in chronic schizophrenia. J. Psychiatr. Res. 2014, 60, 109–116. [Google Scholar] [CrossRef]
- Deckmann, K.; Filipski, K.; Krasteva-Christ, G.; Fronius, M.; Althaus, M.; Rafiq, A.; Papadakis, T.; Renno, L.; Jurastow, I.; Wessels, L.; et al. Bitter triggers acetylcholine release from polymodal urethral chemosensory cells and bladder reflexes. Proc. Natl. Acad. Sci. USA 2014, 111, 8287–8292. [Google Scholar] [CrossRef] [Green Version]
- Wendell, S.; Wang, X.; Brown, M.; Cooper, M.E.; DeSensi, R.S.; Weyant, R.J.; Crout, R.; McNeil, D.W.; Marazita, M.L. Taste genes associated with dental caries. J. Dent. Res. 2010, 89, 1198–1202. [Google Scholar] [CrossRef] [PubMed]
- Glanville, E.V.; Kaplan, A.R. Food preference and sensitivity of taste for bitter compounds. Nature 1965, 205, 851–853. [Google Scholar] [CrossRef]
- Duffy, V.B.; Bartoshuk, L.M. Food acceptance and genetic variation in taste. J. Am. Diet. Assoc. 2000, 100, 647–655. [Google Scholar] [CrossRef]
- Kim, U.K.; Breslin, P.A.; Reed, D.; Drayna, D. Genetics of human taste perception. J. Dent. Res. 2004, 83, 448–453. [Google Scholar] [CrossRef]
- Chamoun, E.; Mutch, D.M.; Allen-Vercoe, E.; Buchholz, A.C.; Duncan, A.M.; Spriet, L.L.; Haines, J.; Ma, D.W.L. Guelph Family Health Study; A review of the associations between single nucleotide polymorphisms in taste receptors, eating behaviors, and health. Crit. Rev. Food Sci. Nutr. 2018, 58, 194–207. [Google Scholar] [CrossRef] [Green Version]
- Dinehart, M.E.; Hayes, J.E.; Bartoshuk, L.M.; Lanier, S.L.; Duffy, V.B. Bitter taste markers explain variability in vegetable sweetness, bitterness, and intake. Physiol. Behav. 2006, 87, 304–313. [Google Scholar] [CrossRef] [PubMed]
- Turner, A.; Veysey, M.; Keely, S.; Scarlett, C.; Lucock, M.; Beckett, E.L. Interactions between bitter taste, diet and dysbiosis: Consequences for appetite and obesity. Nutrients 2018, 10, 1336. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Duffy, V.B.; Davidson, A.C.; Kidd, J.R.; Kidd, K.K.; Speed, W.C.; Pakstis, A.J.; Reed, D.R.; Snyder, D.J.; Bartoshuk, L.M. Bitter receptor gene (TAS2R38), 6-n-propylthiouracil (PROP) bitterness and alcohol intake. Alcohol Clin. Exp. Res. 2004, 28, 1629–1637. [Google Scholar] [CrossRef] [Green Version]
- Cannon, D.S.; Baker, T.B.; Piper, M.E.; Scholand, M.B.; Lawrence, D.L.; Drayna, D.T.; McMahon, W.M.; Villegas, G.M.; Caton, T.C.; Coon, H.; et al. Associations between phenylthiocarbamide gene polymorphisms and cigarette smoking. Nicotine Tob. Res. 2005, 7, 853–858. [Google Scholar] [CrossRef] [Green Version]
- Duffy, V.B. Associations between oral sensation, dietary behaviors and risk of cardiovascular disease (CVD). Appetite 2004, 43, 5–9. [Google Scholar] [CrossRef] [PubMed]
- Ortega, F.J.; Agüera, Z.; Sabater, M.; Moreno-Navarrete, J.M.; Alonso-Ledesma, I.; Xifra, G.; Botas, P.; Delgado, E.; Jimenez-Murcia, S.; Fernández-Garcíaet, J.C.; et al. Genetic variations of the bitter taste receptor TAS2R38 are associated with obesity and impact on single immune traits. Mol. Nutr. Food Res. 2016, 60, 1673–1683. [Google Scholar] [CrossRef]
- Keller, M.; Liu, X.; Wohland, T.; Rohde, K.; Gast, M.T.; Stumvoll, M.; Kovacs, P.; Tonjes, A.; Bottcher, Y. TAS2R38 and its influence on smoking behavior and glucose homeostasis in the German Sorbs. PLoS ONE 2013, 8, e80512. [Google Scholar] [CrossRef] [Green Version]
- Tepper, B.J.; Koelliker, Y.; Zhao, L.; Ullrich, N.V.; Lanzara, C.; d’Adamo, P.; Ferrara, A.; Ulivi, S.; Esposito, L.; Gasparini, P. Variation in the bitter-taste receptor gene TAS2R38, and adiposity in a genetically isolated population in Southern Italy. Obesity 2008, 16, 2289–2295. [Google Scholar] [CrossRef]
- Sharma, K.; Kaur, G.K. PTC bitter taste genetic polymorphism, food choices, physical growth in body height and body fat related traits among adolescent girls from Kangra Valley, Himachal Pradesh (India). Ann. Hum. Biol. 2014, 41, 29–39. [Google Scholar] [CrossRef] [PubMed]
- Deloose, E.; Corsetti, M.; Van Oudenhove, L.; Depoortere, I.; Tack, J. Intragastric infusion of the bitter tastant quinine suppresses hormone release and antral motility during the fasting state in healthy female volunteers. Neurogastroenterol. Motil. 2018, 30. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Iven, J.; Biesiekierski, J.R.; Zhao, D.; Deloose, E.; O’Daly, O.G.; Depoortere, I.; Tack, J.; Van Oudenhove, L. Intragastric quinine administration decreases hedonic eating in healthy women through peptide-mediated gut-brain signaling mechanisms. Nutr. Neurosci. 2018, 22, 850–862. [Google Scholar] [CrossRef] [PubMed]
- Foster-Schubert, K.E.; Overduin, J.; Prudom, C.E.; Liu, J.; Callahan, H.S.; Gaylinn, B.D.; Thorner, M.O.; Cummings, D.E. Acyl and total ghrelin are suppressed strongly by ingested proteins, weakly by lipids, and biphasically by carbohydrates. J. Clin. Endocrinol. Metab. 2008, 93, 1971–1979. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, Q.; Liszt, K.I.; Deloose, E.; Canovai, E.; Thijs, T.; Farré, R.; Ceulemans, L.J.; Lannoo, M.; Tack, J.; Depoortere, I. Obesity alters adrenergic and chemosensory signaling pathways that regulate ghrelin secretion in the human gut. FASEB J. 2019, 33, 4907–4920. [Google Scholar] [CrossRef]
- Liszt, K.I.; Ley, J.P.; Lieder, B.; Behrens, M.; Stöger, V.; Reiner, A.; Hochkogler, C.M.; Köck, E.; Marchiori, A.; Hans, J.; et al. Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells. Proc. Natl. Acad. Sci. USA 2017, 114, 6260–6269. [Google Scholar] [CrossRef] [Green Version]
- Xie, C.; Wang, X.; Young, R.L.; Horowitz, M.; Rayner, C.K.; Wu, T. Role of intestinal bitter sensing in enteroendocrine hormone secretion and metabolic control. Front. Endocrinol. 2018, 9, 1–10. [Google Scholar] [CrossRef]
- Dotson, C.D.; Zhang, L.; Xu, H.; Shin, Y.K.; Vigues, S.; Ott, S.H.; Elson, A.E.T.; Choi, H.J.; Shaw, H.; Egan, J.M.; et al. Bitter taste receptors influence glucose homeostasis. PLoS ONE 2008, 3, e3974. [Google Scholar] [CrossRef] [Green Version]
- Dotson, C.D.; Vigues, S.; Steinle, N.I.; Munger, S.D. T1R and T2R receptors: The modulation of incretin hormones and potential targets for the treatment of type 2 diabetes mellitus. Curr. Opin. Investig. Drugs 2010, 11, 447–454. [Google Scholar]
- Pham, H.; Hui, H.; Morvaridi, S.; Cai, J.; Zhang, S.; Tan, J.; Wu, V.; Levin, N.; Knudsen, B.; Goddard, W.A., 3rd; et al. A bitter pill for type 2 diabetes? The activation of bitter taste receptor TAS2R38 can stimulate GLP-1 release from enteroendocrine L-cells. Biochem. Biophys. Res. Commun. 2016, 475, 295–300. [Google Scholar] [CrossRef] [Green Version]
- Campa, D.; de Rango, F.; Carrai, M.; Crocco, P.; Montesanto, A.; Canzian, F.; Rose, G.; Rizzato, C.; Passarino, G.; Barale, R. Bitter Taste Receptor Polymorphisms and Human Aging. PLoS ONE 2012, 7, e45232. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Melis, M.; Errigo, A.; Crnjar, R.; Pes, G.M.; Tomassini Barbarossa, I. TAS2R38 bitter taste receptor and attainment of exceptional longevity. Sci. Rep. 2019, 9, 1–9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Singh, N.; Shaik, F.A.; Myal, Y.; Chelikani, P. Chemosensory bitter taste receptors T2R4 and T2R14 activation attenuates proliferation and migration of breast cancer cells. Mol. Cell. Biochem. 2020, 465, 199–214. [Google Scholar] [CrossRef] [PubMed]
- Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Martin, L.T.P.; Nachtigal, M.W.; Selman, T.; Nguyen, E.; Salsman, J.; Dellaire, G.; Dupré, D.J. Bitter taste receptors are expressed in human epithelial ovarian and prostate cancers cells and noscapine stimulation impacts cell survival. Mol. Cell. Biochem. 2019, 454, 203–214. [Google Scholar] [CrossRef] [PubMed]
- Wölfle, U.; Haarhaus, B.; Kersten, A.; Fiebich, B.; Hug, M.J.; Schempp, C.M. Salicin from willow bark can modulate neurite outgrowth in human neuroblastoma SH- SY5Y cells. Phytother. Res. 2015, 29, 1494–1500. [Google Scholar] [CrossRef] [PubMed]
- Gaida, M.M.; Mayer, C.; Dapunt, U.; Stegmaier, S.; Schirmacher, P.; Wabnitz, G.H.; Hänsch, G.M. Expression of the bitter receptor T2R38 in pancreatic cancer: Localization in lipid droplets and activation by a bacteria-derived quorum-sensing molecule. Oncotarget 2016, 7, 12623–12632. [Google Scholar] [CrossRef] [Green Version]
- Yamaki, M.; Saito, H.; Isono, K.; Goto, T.; Shirakawa, H.; Shoji, N.; Satoh-Kuriwada, S.; Sasano, T.; Okada, R.; Kudohet, K.; et al. Genotyping analysis of bitter-taste receptor genes TAS2R38 and TAS2R46 in Japanese patients with gastrointestinal cancers. J. Nutr. Sci. Vitaminol. (Tokyo) 2017, 63, 148–154. [Google Scholar] [CrossRef] [Green Version]
- Schembre, S.M.; Cheng, I.; Wilkens, L.R.; Albright, C.L.; Marchand le, L. Variations in bitter-taste receptor genes, dietary intake, and colorectal adenoma risk. Nutr. Cancer 2013, 65, 982–990. [Google Scholar] [CrossRef] [Green Version]
- Choi, J.H.; Kim, J. TAS2R38 Bitterness Receptor Genetic Variation and Risk of Gastrointestinal Neoplasm: A Meta-Analysis. Nutr. Cancer 2019, 71, 585–593. [Google Scholar] [CrossRef] [Green Version]
- Tsutsumi, R.; Goda, M.; Fujimoto, C.; Kanno, K.; Nobe, M.; Kitamura, Y.; Abe, K.; Kawai, M.; Matsumoto, H.; Sakaiet, T.; et al. Effects of chemotherapy on gene expression of lingual taste receptors in patients with head and neck cancer. Laryngoscope 2016, 126, E103–E109. [Google Scholar] [CrossRef] [PubMed]
- Dotson, C.D.; Wallace, M.R.; Bartoshuk, L.M.; Logan, H.L. Variation in the gene TAS2R13 is associated with differences in alcohol consumption in patients with head and neck cancer. Chem. Senses 2012, 37, 737–744. [Google Scholar] [CrossRef] [PubMed]
Author | Tissue | TAS2R | Method | Main Outcome |
---|---|---|---|---|
Mennella 2005 [13] | buccal mucosa cells | TAS2R38 | qRT-PCR | Genotypes at the TAS2R38 locus were significantly related to preferences for sucrose and sweet-tasting beverages and foods, such as cereals, in children but not in adults. |
Rozengurt 2006 [14] | cultured intestinal HuTu-80 and NCI-H716 cell lines | TAS2R3/4/5 TAS2R10/13/14 TAS2R38/39 TAS2R39 TAS2R40/42/43/44/45/46/47 TAS2R50 TAS2R60 | qRT-PCR | NCI-H716 and HuTu-80 express transcripts that encode the GI peptides PYY and GIP and the precursor for glucagon/GLP-1, and its secretion may be via TAS2R receptors. |
Shah 2009 [15] | airway epithelium | TAS2R4 TAS2R38 TAS2R43/46 | qRT-PCR | TAS2Rs are localised in cilia, and their signalling pathway is functional. |
Deshpande 2010 [16] | cultured airway smooth muscle (ASM) | TAS2R10/14 TAS2R31 | qRT-PCR | Bitter tastant induces bronchodilatory effect mediated by TAS2Rs. |
Le Neve 2010 [17] | duodenal cell line HuTu-80 | TAS2R7 TAS2R14 | qRT-PCR | H.g.-12, a steroid glycoside purified from H. gordonii extract, activates human bitter receptors TAS2R7 and TAS2R14. |
Jeon 2011 [18] | epithelial colorectal cell line Caco-2 | TAS2R38 | qRT-PCR | Phenylthiocarbamide was found to increase ATP-binding cassette B1 expression and increases its efflux activity. |
Lee 2012 [19] | sinonasal epithelial cells | TAS2R38 | qRT-PCR | The TAS2R38 genotype represents a defining characteristic in respiratory innate defence that contributes to the complex genetic and environmental interactions predisposing humans to upper respiratory infections. |
Grassin-Delyle 2013 [20] | lung tissue | TAS2R5/7 TAS2R10/14 TAS2R38/39 TAS2R43 | qRT-PCR | TAS2R5, 10 and 14 are involved in the relaxation of human bronchi. |
Orsmark-Pietras 2013 [21] | WBC from children with severe asthma and WBC from healthy children | TAS2R4/5, TAS2R10/13/14/19 TAS2R20 TAS2R31 TAS2R45/46 TAS2R50 | qRT-PCR | The expression of most bitter taste receptors was higher in children with severe asthma compared to the healthy controls, and these differences reached statistical significance for TAS2R13, TAS2R14 and TAS2R19. The expression of all bitter taste receptors was significantly greatest in the lymphocyte population compared to monocytes. |
Foster 2013 [22] | heart tissue | TAS2R3/4/5 TAS2R13/14/19(48) TAS2R20(49) TAS2R30/31 TAS2R43/45/46 TAS2R50 | qRT-PCR | TAS2R14 was the most expressed TAS2R in human heart tissue. |
Lund 2013 [23] | mesenchymal stromal cells (MSC) | TAS2R46 | qRT-PCR | Human bone marrow expresses the TAS2R46 receptor, and it is functional. |
Singh 2014 [24] | mammary epithelial cell lines MCF-10A, MCF-7 and MDA-MB-231 | TAS2R1/4 TAS2R10 TAS2R20(49) TAS2R38 | qRT-PCR | TAS2R4 was the highest expressed TAS2R in normal mammary epithelial cells compared to breast cancer cells. |
Ekoff 2014 [25] | cord blood-derived mast cells (CBMCs) and the mast cell line HMC1.2 | TAS2R3/4/5 TAS2R10/14/19 TAS2R20(49) TAS2R46 | qRT-PCR | TAS2Rs mediated significant inhibition of the release of histamine and PGD2 from IgE-receptor-activated primary human mast cells. The TAS2Rs may mediate anti-inflammatory responses. |
Clark 2015 [26] | thyroid cells, thyrocyte line Nthy Ori 3-1 | TAS2R4 TAS2R10 TAS2R38 TAS2R42/43 | qRT-PCR | TAS2R42 is associated with differences in the circulating levels of thyroid hormones. |
Yu 2015 [27] | enteroendocrine NCI-H716 cells | TAS2R38 | qRT-PCR | GLP-1 secretion was significantly increased by berberine incubation, which was concentration-dependently inhibited by the TAS2R38 antibody. |
Wölfle 2015 [28] | primary keratinocytes (HPKs), keratinocyte cell line HaCaT | TAS2R1 TAS2R38 | qRT-PCR | TAS2R expression was shown throughout the epidermis, but it was weak in the basal cells. |
Wölfle 2016 [29] | placental cell line JEG-3 | TAS2R38 | qRT-PCR | The expression of fully functional TAS2R38 receptors was found in placental tissue. |
Jaggupilli 2017 [30] | cystic fibrosis bronchial epithelial cells (CuFi-1) normal bronchial epithelial cells (NuLi-1) | TAS2R3/4/5 TAS2R10/13/14/19(48) TAS2R320(49) | qRT-PCR | The expression of TAS2R14 and TAS2R20 (49) is much higher in breast cancer cells than in normal mammary tissue. |
airway smooth muscle cells (ASM) | TAS2R14 TAS2R20(49) TAS2R50 | |||
pulmonary artery smooth muscle (PASM) | TAS2R14 TAS2R20(49) TAS2R50 | |||
mammary epithelial cells MCF-10A | TAS2R14 TAS2R20(49) | |||
breast cancer cells MDA-MB-231 | TAS2R14 TAS2R20(49) | |||
Latorre 2016 [31] | colonic mucosal calls | TAS2R38 | qRT-PCR | TAS2R38 is expressed by the human colonic mucosa, where it is localised to distinct types of enteroendocrine cells (EEC), including cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) cells. |
Zheng 2017 [32] | myometrial cells, hTERT-HM cells | TAS2R1/3/4/5/7/8/9 TAS2R10/13/14/16/19 TAS2R20 TAS2R30/31/38/39 TAS2R40 | qRT-PCR | Human myometrial cells express TAS2Rs and the activation of the canonical TAS2R signalling system by bitter tastants in myometrial cells produces profound relaxation of the myometrium. |
Hariri 2017 [33] | sinonasal tissue | TAS2R14 TAS2R38 | qRT-PCR | Flavones activate TAS2R14 expression in sinonasal epithelial cell cilia. |
Freud 2018 [34] | sinonasal tissue | TAS2R4 TAS2R14/16 TAS2R38 | qRT-PCR | All examined TAS2Rs are activated by bacterial ligands. |
Shaw 2018 [35] | skin cells | TAS2R3/4/5/9 TAS2R13/14/16/19 TAS2R20 TAS2R30/31/38/39 TAS2R40/41/42/43/45/46 TAS2R50 TAS2R60 | qRT-PCR | There are differences in TAS2R expression in the skin concerning sun exposure, sex and age. |
Grassin-Delyle 2019 [36] | lung macrophages (LM) | TAS2R3/4/5/7/8/9 TAS2R10/14/19 TAS2R20 TAS2R31/38/39 TAS2R43/45/46 | qRT-PCR | TAS2Rs are expressed in human LMs, and TAS2R agonists inhibit LPS-induced cytokine release by LMs—a process that is not mediated by the release of IL-10. |
Cont 2019 [37] | buccal mucosa | TAS2R38 | qRT-PCR | Infants insensitive to bitter taste (AVI/AVI) were more likely to consume the whole first complementary food meal at the first attempt, compared to sensitive ones (AVI/PAV or PAV/PAV). |
Governini 2020 [38] | semen cells, testicular tissue | TAS2R3/4 TAS2R14/19 TAS2R43 | ddPCR | TAS2R14 is the most expressed bitter receptor subtype in both testis tissue and sperm cells. In vitro capacitation significantly affects the expression and the subcellular localisation of TAS2R receptors in isolated spermatozoa. |
Author | Study Group | Pathological Condition | Tissue | PAV/PAV | PAV/AVI | AVI/AVI |
---|---|---|---|---|---|---|
Adappa 2013 [70] | 28 | CRS | sinonasal tissue samples | 1 | 14 | 13 |
Adappa 2014 [71] | 70 | CRS | sinonasal tissue samples | 6 | 38 | 26 |
Adappa 2016 [72] | 123 | CRS | sinonasal tissue samples | 27 | 96 | |
Dżaman 2016 [73] | 20 | CRS | blood | 4 | 10 | 6 |
Gallo 2016 [77] | 53 | CRS | blood | 8 | 32 | 13 |
Adappa 2016 [78] | 49 | CF | sinonasal tissue samples | 7 | 24 | 18 |
Cohen 2017 [76] | 28 | CRS | sinonasal tissue samples | 1 | 14 | 13 |
Cantone 2018 [74] | 124 | CRS | saliva blood | 2 | 32 | 31 |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Jeruzal-Świątecka, J.; Fendler, W.; Pietruszewska, W. Clinical Role of Extraoral Bitter Taste Receptors. Int. J. Mol. Sci. 2020, 21, 5156. https://doi.org/10.3390/ijms21145156
Jeruzal-Świątecka J, Fendler W, Pietruszewska W. Clinical Role of Extraoral Bitter Taste Receptors. International Journal of Molecular Sciences. 2020; 21(14):5156. https://doi.org/10.3390/ijms21145156
Chicago/Turabian StyleJeruzal-Świątecka, Joanna, Wojciech Fendler, and Wioletta Pietruszewska. 2020. "Clinical Role of Extraoral Bitter Taste Receptors" International Journal of Molecular Sciences 21, no. 14: 5156. https://doi.org/10.3390/ijms21145156
APA StyleJeruzal-Świątecka, J., Fendler, W., & Pietruszewska, W. (2020). Clinical Role of Extraoral Bitter Taste Receptors. International Journal of Molecular Sciences, 21(14), 5156. https://doi.org/10.3390/ijms21145156