T2R

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T2R (synonymous TAS2R ) is a group of proteins that are receptors for the bitter taste .

properties

T2R belong to the group of G-protein-coupled receptors . They are heptahelical receptors of around 300 to 330 amino acids . To date, 29 different isoforms of T2R have been described in humans . T2Rs are produced in a variety of tissues , including the mouth , nose , lungs , heart , stomach, and intestines . Activation of the T2R on the tongue creates the bitter taste. In humans, T2R16 and T2R38 play a major role in the perception of the bitter taste.

T2R are also involved in the antimicrobial immune response in the respiratory tract by modulating the production of pro-inflammatory cytokines by macrophages and mast cells and by inhibiting inflammation of the lungs. Bitter substances lead to bronchodilation in the smooth muscles of the upper respiratory tract and to an increased beat frequency of the cilia of the epithelial cells of the lungs. A polymorphism in the gene for T2R38 is associated with an increased risk of chronic rhinosinusitis . Phenylthiocarbamide is a selective agonist for T2R38.

Signal transduction

The signal transduction upon activation of T2R via activation of G-proteins . As a result, the phospholipase C PLC-β2 is activated, whereby the secondary messenger substances IP 3 and diacylglycerol are formed from PIP 2 . This is followed by activation of the IP3 receptor and an increase in Ca 2+ in the cytosol , whereupon the ion channel TRPM5 is activated. Various inhibitors for T2R have been described.

Individual evidence

  1. ↑ AA Bachmanov, GK Beauchamp: key receptor genes. In: Annual review of nutrition. Volume 27, 2007, pp. 389-414, doi : 10.1146 / annurev.nutr.26.061505.111329 , PMID 17444812 , PMC 2721271 (free full text).
  2. ↑ a b c d e P. Devillier, E. Naline, S. Grassin-Delyle: The pharmacology of bitter taste receptors and their role in human airways. In: Pharmacology & therapeutics. Volume 155, November 2015, pp. 11-21, doi : 10.1016 / j.pharmthera.2015.08.001 , PMID 26272040 .
  3. ↑ a b c d e F. A. Shaik, N. Singh, M. Arakawa, K. Duan, RP Bhullar, P. Chelikani: Bitter taste receptors: Extraoral roles in pathophysiology. In: The international journal of biochemistry & cell biology. Volume 77, Pt B08 2016, pp. 197-204, doi : 10.1016 / j.biocel.2016.03.011 , PMID 27032752 .
  4. ↑ a b c d C. D. Dotson, S. Vigues, NI Steinle, SD Munger: T1R and T2R receptors: the modulation of incretin hormones and potential targets for the treatment of type 2 diabetes mellitus. In: Current opinion in investigational drugs. Volume 11, Number 4, April 2010, pp. 447-454, PMID 20336593 , PMC 4535793 (free full text).
  5. ^ AS Khan, B. Murtaza, A. Hichami, NA Khan: A cross-talk between fat and bitter taste modalities. In: Biochemistry. [Electronic publication before printing] June 2018, doi : 10.1016 / j.biochi.2018.06.013 , PMID 29936293 .
  6. ^ RJ Lee, NA Cohen: Role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis. In: Current opinion in allergy and clinical immunology. Volume 15, number 1, February 2015, pp. 14-20, doi : 10.1097 / ACI.0000000000000120 , PMID 25304231 , PMC 5902169 (free full text).
  7. ↑ V. Triantafillou, AD Workman, MA Kohanski, NA Cohen: Taste Receptor Polymorphisms and Immune Response: A Review of Receptor Genotypic-Phenotypic Variations and Their Relevance to Chronic Rhinosinusitis. In: Frontiers in cellular and infection microbiology. Volume 8, 2018, p. 64, doi : 10.3389 / fcimb.2018.00064 , PMID 29564227 , PMC 5845873 (free full text).
  8. ↑ B. Bufe, PA Breslin, C. Kuhn, DR Reed, CD Tharp, JP Slack, UK Kim, D. Drayna, W. Meyerhof: The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception. In: Current biology: CB. Volume 15, Number 4, February 2005, pp. 322-327, doi : 10.1016 / j.cub.2005.01.047 , PMID 15723792 , PMC 1400547 (free full text).
  9. ↑ A. Jaggupilli, R. Howard, JD Upadhyaya, RP Bhullar, P. Chelikani: Bitter taste receptors: Novel insights into the biochemistry and pharmacology. In: The international journal of biochemistry & cell biology. Volume 77, Pt B08 2016, pp. 184-196, doi : 10.1016 / j.biocel.2016.03.005 , PMID 26995065 .