{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:09:02Z","timestamp":1790791742548,"version":"4.1.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Over thousands of years of evolution, animals have developed many ways to protect themselves. One of the most protective ways to avoid disease is to prevent the absorption of harmful components. This protective function is a basic role of bitter taste receptors (TAS2Rs), a G protein-coupled receptor family, whose presence in extraoral tissues has intrigued many researchers. In humans, there are 25 TAS2Rs, and although we know a great deal about some of them, others are still shrouded in mystery. One in this latter category is bitter taste receptor 39 (TAS2R39). Besides the oral cavity, it has also been found in the gastrointestinal tract and the respiratory, nervous and reproductive systems. TAS2R39 is a relatively non-selective receptor, which means that it can be activated by a range of mostly plant-derived compounds such as theaflavins, catechins and isoflavones. On the other hand, few antagonists for this receptor are available, since only some flavones have antagonistic properties (all of them detailed in the document). The primary role of TAS2R39 is to sense the bitter components of food and protect the organism from harmful compounds. There is also some indication that this bitter taste receptor regulates enterohormones and in turn, regulates food intake. In the respiratory system, it may be involved in the congestion process of allergic rhinitis and may stimulate inflammatory cytokines. However, more thorough research is needed to determine the precise role of TAS2R39 in these and other tissues.<\/jats:p>","DOI":"10.3389\/fendo.2022.854718","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T05:03:42Z","timestamp":1646715822000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":33,"title":["The Hidden One: What We Know About Bitter Taste Receptor 39"],"prefix":"10.3389","volume":"13","author":[{"given":"Florijan","family":"Jal\u0161evac","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximena","family":"Terra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Rodr\u00edguez-Gallego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"Beltran-Deb\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Blay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Pinent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ard\u00e9vol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05401","article-title":"The Receptors and Cells for Mammalian Taste","volume":"444","author":"Chandrashekar","year":"2006","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1016\/j.neuron.2020.03.006","article-title":"All-Electrical Ca2+-Independent Signal Transduction Mediates Attractive Sodium Taste in Taste Buds","volume":"106","author":"Nomura","year":"2020","journal-title":"Neuron"},{"key":"B3","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.cell.2019.08.031","article-title":"Sour Sensing From the Tongue to the Brain","volume":"179","author":"Zhang","year":"2019","journal-title":"Cell"},{"key":"B4","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1515\/cmble-2015-0042","article-title":"How Taste Works: Cells, Receptors and Gustatory Perception","volume":"20","author":"Kikut-Ligaj","year":"2015","journal-title":"Cell Mol Biol Lett"},{"key":"B5","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1146\/annurev-biochem-060614-033910","article-title":"The Molecular Basis of G Protein-Coupled Receptor Activation","volume":"87","author":"Weis","year":"2018","journal-title":"Annu Rev Biochem"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gat009","article-title":"Taste Perception: From the Tongue to the Testis","volume":"19","author":"Li","year":"2013","journal-title":"Mol Hum Reprod"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2174\/13816128113199990566","article-title":"Genetics of Taste Receptors","volume":"20","author":"Bachmanov","year":"2014","journal-title":"Curr Pharm Des"},{"key":"B8","doi-asserted-by":"publisher","first-page":"4423","DOI":"10.3390\/molecules25194423","article-title":"Structure-Function Analyses of Human Bitter Taste Receptors\u2014Where do We Stand","volume":"25","author":"Behrens","year":"2020","journal-title":"Molecules"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.10.001","article-title":"Common Sense About Taste: From Mammals to Insects","volume":"139","author":"Yarmolinsky","year":"2009","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/chemse\/bjp092","article-title":"The Molecular Receptive Ranges of Human TAS2R Bitter Taste Receptors","volume":"35","author":"Meyerhof","year":"2009","journal-title":"Chem Senses"},{"key":"B11","volume-title":"TAS2R39 Gene - GeneCards | T2R39 Protein | T2R39 Antibody","year":""},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1168-07.2007","article-title":"Gustatory Expression Pattern of the Human TAS2R Bitter Receptor Gene Family Reveals a Heterogenous Population of Bitter Responsive Taste Receptor Cells","volume":"27","author":"Behrens","year":"2007","journal-title":"J Neurosci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-215087","article-title":"Extraoral Bitter Taste Receptors as Mediators of Off-Target Drug Effects","volume":"26","author":"Clark","year":"2012","journal-title":"FASEB J"},{"key":"B14","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1111\/cea.12727","article-title":"Increased Expression of Bitter Taste Receptors in Human Allergic Nasal Mucosa and Their Contribution to the Shrinkage of Human Nasal Mucosa","volume":"46","author":"Kook","year":"2016","journal-title":"Clin Exp Allergy"},{"key":"B15","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.physbeh.2011.02.010","article-title":"Gustatory and Extragustatory Functions of Mammalian Taste Receptors","volume":"105","author":"Behrens","year":"2011","journal-title":"Physiol Behav"},{"key":"B16","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1152\/ajpgi.00074.2006","article-title":"Colocalization of the \u03b1-Subunit of Gustducin With PYY and GLP-1 in L Cells of Human Colon","volume":"291","author":"Rozengurt","year":"2006","journal-title":"Am J Physiol - Gastrointest Liver Physiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-14-134","article-title":"The Expression and Relaxant Effect of Bitter Taste Receptors in Human Bronchi","volume":"14","author":"Grassin-Delyle","year":"2013","journal-title":"Respir Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.lfs.2016.11.010","article-title":"The Expression of Bitter Taste Receptors in Mesenteric, Cerebral and Omental Arteries","volume":"170","author":"Chen","year":"2017","journal-title":"Life Sci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e0205322","DOI":"10.1371\/journal.pone.0205322","article-title":"Personalized Expression of Bitter \u201cTaste\u201d Receptors in Human Skin","volume":"13","author":"Shaw","year":"2018","journal-title":"PloS One"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201601323RR","article-title":"Bitter Taste Receptors as Targets for Tocolytics in Preterm Labor Therapy","volume":"31","author":"Zheng","year":"2017","journal-title":"FASEB J"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01267","article-title":"Bitter Taste Receptors (TAS2Rs) in Human Lung Macrophages: Receptor Expression and Inhibitory Effects of TAS2R Agonists","volume":"10","author":"Grassin-Delyle","year":"2019","journal-title":"Front Physiol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.113953","article-title":"The Bitter Taste Receptor TAS2R14 Regulates Resveratrol Transport Across the Human Blood-Cerebrospinal Fluid Barrier","volume":"177","author":"Duarte","year":"2020","journal-title":"Biochem Pharmacol"},{"key":"B23","volume-title":"Tissue Expression of TAS2R39 - Summary - The Human Protein Atlas","year":""},{"key":"B24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0118200","article-title":"Snooker Structure-Based Pharmacophore Model Explains Differences in Agonist and Blocker Binding to Bitter Receptor Htas2r39","volume":"10","author":"Roland","year":"2015","journal-title":"PloS One"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1021\/jf202816u","article-title":"Soy Isoflavones and Other Isoflavonoids Activate the Human Bitter Taste Receptors Htas2r14 and Htas2r39","volume":"59","author":"Roland","year":"2011","journal-title":"J Agric Food Chem"},{"key":"B26","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/381796a0","article-title":"Transduction of Bitter and Sweet Taste by Gustducin","volume":"381","author":"Wong","year":"1996","journal-title":"Nature"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1177\/00220345980770040601","article-title":"Gustducin and its Role in Taste","volume":"77","author":"Spielman","year":"1998","journal-title":"J Dent Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/s0021-9258(19)50304-0","article-title":"Primary Structure and Cell-Type Specific Expression of a Gustatory G Protein-Coupled Receptor Related to Olfactory Receptors","volume":"268","author":"Abe","year":"1993","journal-title":"J Biol Chem"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-08-02852.1997","article-title":"Differential Expression of-Gustducin in Taste Bud Populations of the Rat and Hamster","volume":"17","author":"Boughter","year":"1997","journal-title":"J Neurosci"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.68","article-title":"Taste Buds: Cells, Signals and Synapses","volume":"18","author":"Roper","year":"2017","journal-title":"Nat Rev Neurosci"},{"key":"B31","article-title":"Anatomy and Development of the Human Taste System","volume-title":"Handbook of Clinical Neurology","author":"Witt","year":"2019"},{"key":"B32","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00424-020-02464-4","article-title":"Taste Transduction and Channel Synapses in Taste Buds","volume":"473","author":"Taruno","year":"2021","journal-title":"Pflugers Arch"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms21145156","article-title":"Clinical Role of Extraoral Bitter Taste Receptors","volume":"21","author":"Jeruzal-\u015awi\u0105tecka","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.587664","article-title":"G Protein-Coupled Receptors in Taste Physiology and Pharmacology","volume":"11","author":"Ahmad","year":"2020","journal-title":"Front Pharmacol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1074\/jbc.R100054200","article-title":"Molecular Mechanisms of Bitter and Sweet Taste Transduction","volume":"277","author":"Margolskee","year":"2002","journal-title":"J Biol Chem"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1080\/09168451.2014.930326","article-title":"The Human Bitter Taste Receptor Htas2r39 is the Primary Receptor for the Bitterness of Theaflavins","volume":"78","author":"Yamazaki","year":"2014","journal-title":"Biosci Biotechnol Biochem"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.01.079","article-title":"Evaluation of the Bitterness of Green Tea Catechins by a Cell-Based Assay With the Human Bitter Taste Receptor Htas2r39","volume":"405","author":"Narukawa","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1021\/jf403387p","article-title":"Bitter Taste Receptor Activation by Flavonoids and Isoflavonoids: Modeled Structural Requirements for Activation of Htas2r14 and Htas2r39","volume":"61","author":"Roland","year":"2013","journal-title":"J Agric Food Chem"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.683627","article-title":"Vanillin Activates Human Bitter Taste Receptors TAS2R14, TAS2R20, and TAS2R39","volume":"8","author":"Morini","year":"2021","journal-title":"Front Nutr"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-009-8755-9","article-title":"Bitter Peptides and Bitter Taste Receptors","volume":"66","author":"Maehashi","year":"2009","journal-title":"Cell Mol Life Sci"},{"key":"B41","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1021\/jf303146h","article-title":"Amino Acids and Peptides Activate at Least Five Members of the Human Bitter Taste Receptor Family","volume":"61","author":"Kohl","year":"2013","journal-title":"J Agric Food Chem"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0094451","article-title":"6-Methoxyflavanones as Bitter Taste Receptor Blockers for Htas2r39","volume":"9","author":"Roland","year":"2014","journal-title":"PloS One"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1271\/BBB.130329","article-title":"Activation of the Htas2r14 Human Bitter-Taste Receptor by (-)-Epigallocatechin Gallate and (-)-Epicatechin Gallate","volume":"77","author":"Yamazaki","year":"2013","journal-title":"Biosci Biotechnol Biochem"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.100893","article-title":"Human Bitter Taste Receptors Htas2r8 and Htas2r39 With Differential Functions to Recognize Bitter Peptides","volume":"75","author":"Ueno","year":"2011","journal-title":"Biosci Biotechnol Biochem"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2020.135041","article-title":"Effects of Bitter Receptor Antagonists on Behavioral Lick Responses of Mice","volume":"730","author":"Masamoto","year":"2020","journal-title":"Neurosci Lett"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00030.2005","article-title":"Genomic Organization, Expression, and Function of Bitter Taste Receptors (T2R) in Mouse and Rat","volume":"22","author":"Wu","year":"2005","journal-title":"Physiol Genomics"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.718544","article-title":"Comprehensive Analysis of Mouse Bitter Taste Receptors Reveals Different Molecular Receptive Ranges for Orthologous Receptors in Mice and Humans","volume":"291","author":"Lossow","year":"2016","journal-title":"J Biol Chem"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.13140\/RG.2.2.11735.91045","article-title":"Study on the Effects of Bitter Taste Receptor Agonists on the Rat Pulmonary Artery","author":"Alshehri","year":"2020"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90514.2008","article-title":"Secretory Effects of a Luminal Bitter Tastant and Expressions of Bitter Taste Receptors, T2Rs, in the Human and Rat Large Intestine","volume":"296","author":"Kaji","year":"2009","journal-title":"Am J Physiol - Gastrointest Liver Physiol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1694","article-title":"The Taste of Toxicity: A Quantitative Analysis of Bitter and Toxic Molecules","volume":"69","author":"Nissim","year":"2017","journal-title":"IUBMB Life"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e3974","DOI":"10.1371\/journal.pone.0003974","article-title":"Bitter Taste Receptors Influence Glucose Homeostasis","volume":"3","author":"Dotson","year":"2008","journal-title":"PloS One"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201600242","article-title":"Subchronic Treatment With Grape-Seed Phenolics Inhibits Ghrelin Production Despite a Short-Term Stimulation of Ghrelin Secretion Produced by Bitter-Sensing Flavanols","volume":"60","author":"Serrano","year":"2016","journal-title":"Mol Nutr Food Res"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2014","article-title":"Ghrelin, CCK, GLP-1, and PYY(3-36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB","volume":"97","author":"Steinert","year":"2017","journal-title":"Physiol Rev"},{"key":"B54","doi-asserted-by":"publisher","first-page":"3784","DOI":"10.3390\/nu12123784","article-title":"Modulation of Food Intake by Differential TAS2R Stimulation in Rat","volume":"12","author":"Grau-Bov\u00e9","year":"2020","journal-title":"Nutrients"},{"key":"B55","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.3390\/nu11092017","article-title":"Taste Receptors in Upper Airway Innate Immunity","volume":"11","author":"Carey","year":"2019","journal-title":"Nutrients"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.854718\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T05:03:47Z","timestamp":1646715827000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.854718\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,8]]},"references-count":55,"alternative-id":["10.3389\/fendo.2022.854718"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.854718","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,8]]},"article-number":"854718"}}