323
Views
6
CrossRef citations to date
0
Altmetric
Reviews

A role for airway taste receptor modulation in the treatment of upper respiratory infections

, , &
Pages 157-170 | Received 02 Nov 2015, Accepted 21 Dec 2015, Published online: 22 Jan 2016

References

  • Papers of special note have been highlighted as:
  • of interest
  • •• of considerable interest
  • Blackwell DL, Lucas JW, Clarke TC. Summary health statistics for U.S. adults: national health interview survey, 2012. Vital Health Stat. 2014;10(260):1–161.
  • Ray NF, Baraniuk JN, Thamer M, et al. Healthcare expenditures for sinusitis in 1996: contributions of asthma, rhinitis, and other airway disorders. J Allergy Clin Immunol. 1999;103(3 Pt 1):408–414.
  • Genoway KA, Philpott CM, Javer AR. Pathogen yield and antimicrobial resistance patterns of chronic rhinosinusitis patients presenting to a tertiary rhinology centre. J Otolaryngol Head Neck Surg. 2011;40(3):232–237.
  • Gliklich RE, Metson R. The health impact of chronic sinusitis in patients seeking otolaryngologic care. Otolaryngol Head Neck Surg. 1995;113(1):104–109.
  • Hopkins C, Gillett S, Slack R, et al. Psychometric validity of the 22-item sinonasal outcome test. Clin Otolaryngol: Official Journal ENT-UK; Official Journal Netherlands Society Oto-Rhino-Laryngology Cervico-Facial Surgery. 2009;34(5):447–454.
  • Lee RJ, Cohen NA. Bitter and sweet taste receptors in the respiratory epithelium in health and disease. J Mol Med (Berl). 2014;92(12):1235–1244.
  • Williams RJ. “Taste deficiency” for creatine. Science. 1931;74(1928):597–598.
  • Fox AL. The relationship between chemical constitution and taste. Proc Natl Acad Sci U S A. 1932;18(1):115–120.

• First account of a perceptual difference of individuals to phenylthiocarbamide.

  • Guo SW, Reed DR. The genetics of phenylthiocarbamide perception. Ann Hum Biol. 2001;28(2):111–142.
  • Olson JM, Boehnke M, Neiswanger K, et al. Alternative genetic models for the inheritance of the phenylthiocarbamide taste deficiency. Genet Epidemiol. 1989;6(3):423–434.
  • Reed DR, Bartoshuk LM, Duffy V, et al. Propylthiouracil tasting: determination of underlying threshold distributions using maximum likelihood. Chem Senses. 1995;20(5):529–533.
  • Conneally PM, Dumont-Driscoll M, Huntzinger RS, et al. Linkage relations of the loci for Kell and phenylthiocarbamide taste sensitivity. Hum Hered. 1976;26(4):267–271.
  • Reed DR, Nanthakumar E, North M, et al. Localization of a gene for bitter-taste perception to human chromosome 5p15. Am J Hum Genet. 1999;64(5):1478–1480.
  • Akesson HO. Taste sensitivity to phenyl-thio-urea in tuberculosis and diabetes mellitus. Ann Hum Genet. 1959;23:262–265.
  • Adler E, Hoon MA, Mueller KL, et al. A novel family of mammalian taste receptors. Cell. 2000;100(6):693–702.
  • Chandrashekar J, Mueller KL, Hoon MA, et al. T2Rs function as bitter taste receptors. Cell. 2000;100(6):703–711.
  • Hoon MA, Adler E, Lindemeier J, et al. Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity. Cell. 1999;96(4):541–551.
  • Bufe B, Breslin PAS, Kuhn C, et al. The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception. Curr Biol. 2005;15(4):322–327.

• Landmark study confirming the molecular basis of individual differences in perception of phenylthiocarbamide.

  • Kinnamon SC. Taste receptor signalling - from tongues to lungs. Acta Physiologica (Oxford, England). 2012;204(2):158–168.
  • Breslin PA, Huang L. Human taste: peripheral anatomy, taste transduction, and coding. Adv Otorhinolaryngol. 2006;63:152–190.
  • Kuhn C, Bufe B, Batram C, et al. Oligomerization of TAS2R bitter taste receptors. Chem Senses. 2010;35(5):395–406.
  • Margolskee RF. The molecular biology of taste transduction. BioEssays: News and Rev in Mol, Cell and Devl Biol. 1993;15(10):645–650.
  • Roudnitzky N, Behrens M, Engel A, et al. Receptor polymorphism and genomic structure interact to shape bitter taste perception. PLoS Genet. 2015;11(9):e1005530.
  • Meyerhof W, Batram C, Kuhn C, et al. The molecular receptive ranges of human TAS2R bitter taste receptors. Chem Senses. 2010;35(2):157–170.

•• Extensive study of the breadth of sensitivity of T2R receptors to both natural and synthetic bitter compounds.

  • Clapp TR, Stone LM, Margolskee RF, et al. Immunocytochemical evidence for co-expression of type III IP3 receptor with signaling components of bitter taste transduction. BMC Neurosci. 2001;2:6.
  • Huang L, Shanker YG, Dubauskaite J, et al. Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium. Nat Neurosci. 1999;2(12):1055–1062.
  • Clapp TR, Trubey KR, Vandenbeuch A, et al. Tonic activity of Galpha-gustducin regulates taste cell responsivity. FEBS Letters. 2008;582(27):3783–3787.
  • Taruno A, Vingtdeux V, Ohmoto M, et al. CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature. 2013;495(7440):223–226.
  • Jiang P, Josue J, Li X, et al. Major taste loss in carnivorous mammals. Proc Natl Acad Sci U S A. 2012;109(13):4956–4961.
  • Mueller KL, Hoon MA, Erlenbach I, et al. The receptors and coding logic for bitter taste. Nature. 2005;434(7030):225–229.
  • Kalmus H. Defective colour vision, PTC tasting, and drepanocytosis in samples from fifteen brazilian populations. Ann Hum Genet. 1957;21(4):313–317.
  • Reed DR, Zhu G, Breslin PA, et al. The perception of quinine taste intensity is associated with common genetic variants in a bitter receptor cluster on chromosome 12. Hum Mol Genet. 2010;19(21):4278–4285.
  • Kim U, Wooding S, Ricci D, et al. Worldwide haplotype diversity and coding sequence variation at human bitter taste receptor loci. Hum Mutat. 2005;26(3):199–204.
  • Zancanaro C, Caretta CM, Merigo F, et al. alpha-Gustducin expression in the vomeronasal organ of the mouse. Eur J Neurosci. 1999;11(12):4473–4475.
  • Clark AA, Liggett SB, Munger SD. Extraoral bitter taste receptors as mediators of off-target drug effects. Faseb J. 2012;26(12):4827–4831.
  • Laffitte A, Neiers F, Briand L. Functional roles of the sweet taste receptor in oral and extraoral tissues. Curr Opin Clin Nutr Metab Care. 2014;17(4):379–385.
  • Depoortere I. Taste receptors of the gut: emerging roles in health and disease. Gut. 2014;63(1):179–190.
  • Clark AA, Dotson CD, Elson AE, et al. TAS2R bitter taste receptors regulate thyroid function. Faseb J. 2015;29(1):164–172.
  • Behrens M, Born S, Redel U, et al. Immunohistochemical detection of TAS2R38 protein in human taste cells. PLoS One. 2012;7(7):e40304.
  • Jang H-J, Kokrashvili Z, Theodorakis MJ, et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A. 2007;104(38):15069–15074.
  • Kyriazis GA, Soundarapandian MM, Tyrberg B. Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion. Proc Natl Acad Sci U S A. 2012;109(8):E524–532.
  • Mennella JA, Spector AC, Reed DR, et al. The bad taste of medicines: overview of basic research on bitter taste. Clin Ther. 2013;35(8):1225–1246.
  • Finger TE, Bottger B, Hansen A, et al. Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration. Proc Natl Acad Sci U S A. 2003;100(15):8981–8986.

•• The first study to identify solitary chemosensory cells in mammals and demonstrate functional T2R expression in the respiratory epithelium.

  • Gulbransen BD, Clapp TR, Finger TE, et al. Nasal solitary chemoreceptor cell responses to bitter and trigeminal stimulants in vitro. J Neurophysiol. 2008;99(6):2929–2937.
  • Tizzano M, Gulbransen BD, Vandenbeuch A, et al. Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Proc Natl Acad Sci. 2010;107(7):3210–3215.

• First study to demonstrate that acyl-homoserine lactones activate murine solitary chemosensory cells via the canonical taste transduction cascade.

  • Tizzano M, Cristofoletti M, Sbarbati A, et al. Expression of taste receptors in solitary chemosensory cells of rodent airways. BMC Pulm Med. 2011;11(1):3.
  • Lee RJ, Kofonow JM, Rosen PL, et al. Bitter and sweet taste receptors regulate human upper respiratory innate immunity. J Clin Invest. 2014;124(3):1393–1405.
  • Cohen NA, Widelitz JS, Chiu AG, et al. Familial aggregation of sinonasal polyps correlates with severity of disease. Otolaryngol Head Neck Surg. 2006;134(4):601–604.
  • Lionakis MS, Netea MG, Holland SM. Mendelian genetics of human susceptibility to fungal infection. Cold Spring Harb Perspect Med. 2014;4:6.
  • Adappa ND, Zhang Z, Palmer JN, et al. The bitter taste receptor T2R38 is an independent risk factor for chronic rhinosinusitis requiring sinus surgery. Int Forum Allergy Rhinol. 2014;4(1):3–7.
  • Ooi EH, Wormald P-J, Tan LW. Innate immunity in the paranasal sinuses: a review of nasal host defenses. Am J Rhinol. 2008;22(1):13–19.
  • Eliezer N, Sade J, Silberberg A, et al. The role of mucus in transport by cilia. Am Rev Respir Dis. 1970;102(1):48–52.
  • Ramanathan M Jr., Lane AP. Innate immunity of the sinonasal cavity and its role in chronic rhinosinusitis. Otolaryngol Head Neck Surg. 2007;136(3):348–356.
  • Lee RJ, Chen B, Doghramji L, et al. Vasoactive intestinal peptide regulates sinonasal mucociliary clearance and synergizes with histamine in stimulating sinonasal fluid secretion. Faseb J. 2013;27(12):5094–5103.
  • Gudis D, Zhao K-Q, Cohen NA. Acquired cilia dysfunction in chronic rhinosinusitis. Am J Rhinol Allergy. 2012;26(1):1–6.
  • Fang FC. Perspectives series: host/pathogen interactions. Mechanisms of nitric oxide-related antimicrobial activity. J Clin Invest. 1997;99(12):2818–2825.
  • Deja M, Busch T, Bachmann S, et al. Reduced nitric oxide in sinus epithelium of patients with radiologic maxillary sinusitis and sepsis. Am J Respir Crit Care Med. 2003;168(3):281–286.
  • Knowles MR, Boucher RC. Mucus clearance as a primary innate defense mechanism for mammalian airways. J Clin Invest. 2002;109(5):571–577.
  • Pearson JP, Passador L, Iglewski BH, et al. A second N-acylhomoserine lactone signal produced by Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 1995;92(5):1490–1494.
  • Lee RJ, Xiong G, Kofonow JM, et al. T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection. J Clin Invest. 2012;122(11):4145–4159.
  • Suh JD, Cohen NA, Palmer JN. Biofilms in chronic rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg. 2010;18(1):27–31.
  • Cohen M, Kofonow J, Nayak JV, et al. Biofilms in chronic rhinosinusitis: a review. Am J Rhinol Allergy. 2009;23(3):255–260.
  • Jimenez PN, Koch G, Thompson JA, et al. The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. Microbiol Mol Biol Rev: MMBR. 2012;76(1):46–65.
  • Lee RJ, Chen B, Redding KM, et al. Mouse nasal epithelial innate immune responses to Pseudomonas aeruginosa quorum-sensing molecules require taste signaling components. Innate Immun. 2014;20(6):606–617.

•• Proof that bitter compounds produced by Pseudomonas aeruginosa stimulate intracellular transduction of taste signaling components in human respiratory epithelium.

  • Sandau MM, Goodman JR, Thomas A, et al. A functional comparison of the domestic cat bitter receptors Tas2r38 and Tas2r43 with their human orthologs. BMC Neurosci. 2015;16:33.
  • Brockhoff A, Behrens M, Massarotti A, et al. 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(15):6236–6243.
  • Tizzano M, Finger TE. Chemosensors in the nose: guardians of the airways. Physiology (Bethesda, Md.). 2013;28(1):51–60.
  • Shah AS, Ben-Shahar Y, Moninger TO, et al. Motile cilia of human airway epithelia are chemosensory. Science. 2009;325(5944):1131–1134.
  • Greene CM, McElvaney NG. Toll-like receptor expression and function in airway epithelial cells. Arch Immunol Ther Exp (Warsz). 2005;53(5):418–427.
  • Ramanathan M Jr., Lane AP. A comparison of experimental methods in molecular chronic rhinosinusitis research. Am J Rhinol. 2007;21(3):373–377.
  • Dimova S, Brewster ME, Noppe M, et al. The use of human nasal in vitro cell systems during drug discovery and development. Toxicology vitro: Int J Published Assoc with BIBRA. 2005;19(1):107–122.
  • Saunders CJ, Christensen M, Finger TE, et al. Cholinergic neurotransmission links solitary chemosensory cells to nasal inflammation. Proc Natl Acad Sci U S A. 2014;111(16):6075–6080.

•• Study establishing that solitary chemosensory cells (SCCs) release acetylcholine to activate neurogenic inflammation and recruit the immune system.

  • Barham HP, Cooper SE, Anderson CB, et al. Solitary chemosensory cells and bitter taste receptor signaling in human sinonasal mucosa. Int Forum Allergy Rhinol. 2013;3(6):450–457.
  • Braun T, Mack B, Kramer MF. Solitary chemosensory cells in the respiratory and vomeronasal epithelium of the human nose: a pilot study. Rhinology. 2011;49(5):507–512.
  • Mennella JA, Pepino MY, Duke FF, et al. Psychophysical dissection of genotype effects on human bitter perception. Chem Senses. 2011;36(2):161–167.
  • Lipchock SV, Mennella JA, Spielman AI, et al. Human bitter perception correlates with bitter receptor messenger RNA expression in taste cells. Am J Clin Nutr. 2013;98(4):1136–1143.
  • Jiang P, Cui M, Zhao B, et al. Lactisole interacts with the transmembrane domains of human T1R3 to inhibit sweet taste. J Biol Chem. 2005;280(15):15238–15246.
  • Jiang P, Cui M, Zhao B, et al. Identification of the cyclamate interaction site within the transmembrane domain of the human sweet taste receptor subunit T1R3. J Biol Chem. 2005;280(40):34296–34305.
  • Kalsi KK, Baker EH, Fraser O, et al. Glucose homeostasis across human airway epithelial cell monolayers: role of diffusion, transport and metabolism. PflüGers Archiv European J Physiol. 2009;457(5):1061–1070.
  • Garnett JP, Baker EH, Baines DL. Sweet talk: insights into the nature and importance of glucose transport in lung epithelium. Eur Respir J. 2012;40(5):1269–1276.
  • Koziel H, Koziel MJ. Pulmonary complications of diabetes mellitus. Pneumonia. Infect Dis Clin North Am. 1995;9(1):65–96.
  • Zhang Z, Adappa ND, Lautenbach E, et al. The effect of diabetes mellitus on chronic rhinosinusitis and sinus surgery outcome. Int Forum Allergy Rhinol. 2014;4(4):315–320.
  • Mfuna Endam L, Filali-Mouhim A, Boisvert P, et al. Genetic variations in taste receptors are associated with chronic rhinosinusitis: a replication study. Int Forum Allergy Rhinol. 2014;4(3):200–206.
  • Adappa ND, Howland TJ, Palmer JN, et al. Genetics of the taste receptor T2R38 correlates with chronic rhinosinusitis necessitating surgical intervention. Int Forum Allergy Rhinol. 2013;3(3):184–187.
  • Xiong Y, Karupiah G, Hogan SP, et al. Inhibition of allergic airway inflammation in mice lacking nitric oxide synthase 2. J Immunol (Baltimore, Md.: 1950). 1999;162(1):445–452.
  • Chennupati SK, Chiu AG, Tamashiro E, et al. Effects of an LL-37-derived antimicrobial peptide in an animal model of biofilm Pseudomonas sinusitis. Am J Rhinol Allergy. 2009;23(1):46–51.
  • Liggett SB, Bitter taste receptors in the wrong place: novel airway smooth muscle targets for treating asthma. Trans Am Clin Climatol Assoc. 2014;125:64–74. discussion 74-65.
  • Settipane RA, Kaliner MA. Chapter 14: nonallergic rhinitis. Am J Rhinol Allergy. 2013;27(Suppl 1):S48–51.
  • Krasteva G, Canning BJ, Hartmann P, et al. Cholinergic chemosensory cells in the trachea regulate breathing. Proc Natl Acad Sci U S A. 2011;108(23):9478–9483.

• Study identifying SCC-like cells in the trachea and establishing that they release acetylcholine to regulate respiratory rate.

  • Saunders CJ, Reynolds SD, Finger TE. Chemosensory brush cells of the trachea. A stable population in a dynamic epithelium. Am J Respir Cell Mol Biol. 2013;49(2):190–196.
  • Gulbransen B, Silver W, Finger TE. Solitary chemoreceptor cell survival is independent of intact trigeminal innervation. J Comp Neurol. 2008;508(1):62–71.
  • Alimohammadi H, Silver WL. Evidence for nicotinic acetylcholine receptors on nasal trigeminal nerve endings of the rat. Chem Senses. 2000;25(1):61–66.
  • Liu L, Chang GQ, Jiao YQ, et al. Neuronal nicotinic acetylcholine receptors in rat trigeminal ganglia. Brain Res. 1998;809(2):238–245.
  • Vijayaraghavan R, Schaper M, Thompson R, et al. Characteristic modifications of the breathing pattern of mice to evaluate the effects of airborne chemicals on the respiratory tract. Arch Toxicol. 1993;67(7):478–490.
  • Saunders CJ, Li WY, Patel TD, et al. Dissecting the role of TRPV1 in detecting multiple trigeminal irritants in three behavioral assays for sensory irritation. F1000Research. 2013;2:74.
  • Lee RJ, Cohen NA. Taste receptors in innate immunity. Cell Mol Life Sci. 2015;72(2):217–236.
  • Lin W, Ogura T, Margolskee RF, et al. TRPM5-expressing solitary chemosensory cells respond to odorous irritants. J Neurophysiol. 2008;99(3):1451–1460.
  • Bernstein JA. Nonallergic rhinitis: therapeutic options. Curr Opin Allergy Clin Immunol. 2013;13(4):410–416.
  • Carey RM, Workman AD, Chen B, et al. Staphylococcus aureus triggers nitric oxide production in human upper airway epithelium. Int Forum Allergy Rhinol. 2015;5(9):808–813.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.