Рецепторы горького вкуса TAS2R как перспективные мишени в персонализированной терапии бронхиальной астмы

В обзоре обобщены современные данные о роли эктопических рецепторов горького вкуса (TAS2R) в патогенезе бронхиальной астмы (БА) в контексте персонализированного подхода к терапии. TAS2R, экспрессируемые в эпителии дыхательных путей, гладкой мускулатуре и иммунокомпетентных клетках, участвуют в ключевых звеньях воспалительного процесса и регуляции бронхиального тонуса. Активация TAS2R приводит к релаксации гладкой мускулатуры дыхательных путей через сигнальные каскады, независимые от β2-адренорецепторов и цАМФ, что обеспечивает эффективность в условиях сниженной чувствительности к β2-агонистам. В Т2-высоком эндотипе БА TAS2R подавляют интерлейкины (ИЛ)-4, ИЛ-5, ИЛ-13, снижая эозинофильное воспаление и дегрануляцию тучных клеток. В не-Т2-вариантах БА рецепторы ингибируют провоспалительные медиаторы (ИЛ-17, ИЛ-8, фактора некроза опухоли α), уменьшают активность нейтрофилов и макрофагов. TAS2R рассматриваются как перспективные фармакологические мишени, особенно в трудно контролируемых формах астмы, резистентных к ингаляционным глюкокортикостероидам. В научной литературе упоминаются исследования препаратов, которые обладают агонистической активностью в отношении TAS2R, и ведутся поиски эндогенных агонистов рецепторов. Представленный материал подчёркивает необходимость дальнейших исследований, направленных на уточнение молекулярных механизмов действия TAS2R, перспективы применения TAS2R-ориентированной терапии при различных эндотипах БА, оценку клинической эффективности и безопасности терапевтических агентов, направленных на персонализацию лечения БА на основе изучения генетических и функциональных особенностей этих рецепторов.

1. Global initiative for asthma (GINA). Global strategy for asthma management and prevention. (Update 2025). URL: https://ginasthma.org/2025-gina-main-report.

2. Byrwa-Hill B.M., Morphew T.L., Presto A.A., Fabisiak J.P., Wenzel S.E. Living in environmental justice areas worsens asthma severity and control: differential interactions with disease duration, age at onset, and pollution // J. Allergy Clin. Immunol. 2023. Vol.152, Iss.5. P.1321–1329.e5. https://doi.org/10.1016/j.jaci.2023.04.015

3. Перельман Ю.М., Перельман Н.Л., Колосов В.П. Качество жизни больных бронхиальной астмой. Владивосток: Дальнаука, 2024. 252 с. ISBN 978-5-8044-1738-4.

4. Федосеев Г.Б. Современное представление о причинах возникновения, особенностях течения и лечения бронхиальной астмы. Актовая речь. Л.: «1ЛМИ им. акад. И.П. Павлова», 1982. С.28.

5. Lai K., Zhan W., Wu F., Zhang Y., Lin L., Li W., Yi F., Jiang Z., Dai Y., Li S., Lin J., Yuan Y., Jiang Y., Qiu C., Zhao L., Chen M., Qiu Z., Li H., Chen R., Luo W., Xie J., Guo C., Jiang M., Yang X., Shi G., Sun D., Chen R., Chung K.F., Shen H., Zhong N. Clinical and inflammatory characteristics of the Chinese APAC cough variant asthma cohort // Front. Med. (Lausanne). 2022. Vol.8. Article number:807385. https://doi.org/10.3389/fmed.2021.807385

6. Ибишева А.Х., Шахгиреева М.Р., Хильдихароева А.Б., Успанова Л.С., Шамсадова С.А., Джабраилова Л.В. Бронхиальная астма в эпоху персонализированной медицины // Сибирский научный медицинский журнал. 2024. Т.44, №6. С.41–47. https://doi.org/10.18699/SSMJ20240604

7. Файзуллина Р.М., Викторов В.В., Гафурова Р.Р. Персонализированная медицина бронхиальной астмы: концепция и перспективы // Вестник Авиценны. 2021. Т.23, №3. С.418–431. https://doi.org/10.25005/2074-0581-2021-23-3-418-431

8. Ray A., Das J., Wenzel S.E. Determining asthma endotypes and outcomes: complementing existing clinical practice with modern machine learning // Cell Rep. Med. 2022. Vol.3, Iss.12. Article number:100857. https://doi.org/10.1016/j.xcrm.2022.100857

9. Авдеев С.Н., Волкова О.А., Демко И.В., Игнатова Г.Л., Лещенко И.В., Канукова Н.А., Куделя Л.М., Невзорова В.А., Недашковская Н.Г., Уханова О.П., Шульженко Л.В., Фассахов Р.С. Организация помощи пациентам с тяжёлой бронхиальной астмой в различных субъектах Российской Федерации. От эндотипов и фенотипов бронхиальной астмы к персонализированному выбору терапии // Терапевтический архив. 2020. Т.92, №2. С.119–123. https://doi.org/10.26442/00403660.2020.02.000555

10. Bourdin A., Brusselle G., Couillard S., Fajt M.L., Heaney L.G., Israel E., McDowell P.J., Menzies-Gow A., Martin N., Mitchell P.D., Petousi N., Quirce S., Schleich F., Pavord I.D. Phenotyping of severe asthma in the era of broad-acting anti-asthma biologics // J. Allergy Clin. Immunol. Pract. 2024. Vol.12, Iss.4. P.809–823. https://doi.org/10.1016/j.jaip.2024.01.023

11. Chung K.F., Dixey P., Abubakar-Waziri H., Bhavsar P., Patel P.H., Guo S., Ji Y. Characteristics, phenotypes, mechanisms and management of severe asthma // Chin. Med. J. 2022. Vol.135, Iss.10. P.1141–1155. https://doi.org/10.1097/CM9.0000000000001990

12. 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. Vol.16, Iss.11. P.1299–1304. https://doi.org/10.1038/nm.2237

13. Harmon C.P., Deng D., Breslin P.A.S. Bitter taste receptors (T2Rs) are sentinels that coordinate metabolic and immunological defense responses // Curr. Opin. Physiol. 2021. Vol.20. P.70–76. https://doi.org/10.1016/j.cophys.2021.01.006

14. Lee R.J., Cohen N.A. Bitter and sweet taste receptors in the respiratory epithelium in health and disease // J. Mol. Med. (Berl.). 2014. Vol. 92, Iss.12. P.1235–1244. https://doi.org/10.1007/s00109-014-1222-6

15. 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. Vol.14, Iss.1. Article number:134. https://doi.org/10.1186/1465-9921-14-134

16. Carey R.M., Lee R.J. Taste receptors in upper airway innate immunity // Nutrients. 2019. Vol.11, Iss.9. Article number:2017. https://doi.org/10.3390/nu11092017

17. Martens K., Steelant B., Bullens D.M.A. Taste receptors: the gatekeepers of the airway epithelium // Cells. 2021. Vol.10, Iss.11. Article number:2889. https://doi.org/10.3390/cells10112889

18. Liggett S.B. Bitter taste receptors on airway smooth muscle as targets for novel bronchodilators // Expert Opin. Ther. Targets. 2013. Vol.17, Iss.6. P.721–731. https://doi.org/10.1517/14728222.2013.782395

19. Kim D., Strzelinski H.R., Liggett S.B. TAS2R5 screening reveals biased agonism that fails to evoke internalization and downregulation resulting in attenuated desensitization // PLoS One. 2025. Vol.20, Iss.2. Article number:e0315820. https://doi.org/10.1371/journal.pone.0315820

20. Tuzim K., Korolczuk A. An update on extra-oral bitter taste receptors // J. Transl. Med. 2021. Vol.19, Iss.1. Article number:440. https://doi.org/10.1186/s12967-021-03067-y

21. Lang T., Di Pizio A., Risso D., Drayna D., Behrens M. Activation profile of TAS2R2, the 26th human bitter taste receptor // Mol. Nutr. Food Res. 2023. Vol.67, Iss.11. Article number:2200775. https://doi.org/10.1002/mnfr.202200775

22. Risso D., Behrens M., Sainz E., Meyerhof W., Drayna D. Probing the evolutionary history of human bitter taste receptor pseudogenes by restoring their function // Mol. Biol. Evol. 2017. Vol.34, Iss.7. P.587–1595. https://doi.org/10.1093/molbev/msx097

23. Zhang M., Chen T., Lu X., Lan X., Chen Z., Lu S. G protein-coupled receptors (GPCRs): advances in structures, mechanisms and drug discovery // Signal Transduct. Target. Ther. 2024. Vol.9, Iss.1. Article number:88. https://doi.org/10.1038/s41392-024-01803-6

24. Cannariato M., Fanunza R., Zizzi E.A., Miceli M., Di Benedetto G., Deriu M.A., Pallante L. Exploring TAS2R46 biomechanics through molecular dynamics and network analysis // Front. Mol. Biosci. 2024. Vol.11. Article number:1473675. https://doi.org/10.3389/fmolb.2024.1473675

25. Woo J.A., Castaño M., Kee T.R., Lee J., Koziol-White C.J., An S.S., Kim D., Kang D.E., Liggett S.B. A Par3/LIM kinase/cofilin pathway mediates human airway smooth muscle relaxation by TAS2R14 // Am. J. Respir. Cell Mol. Biol. 2023. Vol.68, Iss.4. P.417–429. https://doi.org/10.1165/rcmb.2022-0303OC

26. Nayak A.P., Shah S.D., Michael J.V., Deshpande D.A. Bitter taste receptors for asthma therapeutics // Front. Physiol. 2019. Vol.10. Article number:884. https://doi.org/10.3389/fphys.2019.00884

27. Gaida M.M., Dapunt U., Hänsch G.M. Sensing developing biofilms: the bitter receptor T2R38 on myeloid cells // Pathog. Dis. 2016. Vol.74, Iss.3. Article number:ftw004. https://doi.org/10.1093/femspd/ftw004

28. 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. Vol.35, Iss.2. P.157–170. https://doi.org/10.1093/chemse/bjp092

29. 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. Vol.10. Article number:1267. https://doi.org/10.3389/fphys.2019.01267

30. Behrens M. The growing complexity of human bitter taste perception // J. Agric. Food Chem. 2024. Vol.72, Iss.26. P.14530–14534. https://doi.org/10.1021/acs.jafc.4c02465

31. Roelse M., Krasteva N., Pawlizak S., Mai M.K., Jongsma M.A. Tongue-on-a-chip: parallel recording of sweet and bitter receptor responses to sequential injections of pure and mixed sweeteners // J. Agric. Food Chem. 2024. Vol.72, Iss.28. P.15854–15864. https://doi.org/10.1021/acs.jafc.4c00815.

32. Talmon M., Pollastro F., Fresu L.G. The complex journey of the calcium regulation downstream of TAS2R activation // Cells. 2022. Vol.11, Iss.22. Article number:3638. https://doi.org/10.3390/cells11223638

33. Richter P., Andersen G., Kahlenberg K., Mueller A.U., Pirkwieser P., Boger V., Somoza V. Sodium-permeable ion channels TRPM4 and TRPM5 are functional in human gastric parietal cells in culture and modulate the cellular response to bitter-tasting food constituents // J. Agric. Food Chem. 2024. Vol.72, Iss.9. P.4906–4917. https://doi.org/10.1021/acs.jafc.3c09085

34. Yuan G., Jing Y., Wang T., Fernandes V.S., Xin W. The bitter taste receptor agonist-induced negative chronotropic effects on the Langendorff-perfused isolated rat hearts // Eur. J. Pharmacol. 2020. Vol.876. Article number:173063. https://doi.org/10.1016/j.ejphar.2020.173063

35. Kim D., Cho S., Castaño M.A., Panettieri R.A., Woo J.A., Liggett S.B. Biased TAS2R bronchodilators inhibit airway smooth muscle growth by downregulating phosphorylated extracellular signal-regulated kinase 1/2 // Am. J. Respir. Cell Mol. Biol. 2019. Vol.60, Iss.5. P.532–540. https://doi.org/10.1165/rcmb.2018-0189OC

36. 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. 2021. Vol.78, Iss.1. P.271–286. https://doi.org/10.1007/s00018-020-03494-y

37. Agarwal S.L., Deshmankar B.S., Bhargava V. Chloroquine in bronchial asthma // J. Pharm. Pharmacol. 1963. Vol.15, Iss.10. P.693–696. https://doi.org/10.1111/j.2042-7158.1963.tb12862.x

38. Malki A., Fiedler J., Fricke K., Ballweg I., Pfaffl M.W., Krautwurst D. Class I odorant receptors, TAS1R and TAS2R taste receptors, are markers for subpopulations of circulating leukocytes // J. Leukoc. Biol. 2015. Vol.97, Iss.3. P.533–545. https://doi.org/10.1189/jlb.2A0714-331RR

39. Kook J.H., Kim H.K., Kim H.J., Kim K.W., Kim T.H., Kang K.R., Oh D.J., Lee S.H. Increased expression of bitter taste receptors in human allergic nasal mucosa and their contribution to the shrinkage of human nasal mucosa // Clin. Exp. Allergy. 2016. Vol.46, Iss.4. P.584–601. https://doi.org/10.1111/cea.12727

40. Orsmark-Pietras C., James A., Konradsen J.R., Nordlund B., Söderhäll C., Pulkkinen V., Pedroletti C., Daham K., Kupczyk M., Dahlén B., Kere J., Dahlén S.E., Hedlin G., Melén E. Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics // Eur. Respir. J. 2013. Vol.42, Iss.1. P.65–78. https://doi.org/10.1183/09031936.00077712

41. Ni K., Guo J., Bu B., Pan Y., Li J., Liu L., Luo M., Deng L. Naringin as a plant-derived bitter tastant promotes proliferation of cultured human airway epithelial cells via activation of TAS2R signaling // Phytomedicine. 2021. Vol.84. Article number:153491. https://doi.org/10.1016/j.phymed.2021.153491

42. McMahon D.B., Kuek L.E., Johnson M.E., Johnson P.O., Horn R.L.J., Carey R.M., Adappa N.D., Palmer J.N., Lee R.J. The bitter end: T2R bitter receptor agonists elevate nuclear calcium and induce apoptosis in non-ciliated airway epithelial cells // Cell Calcium. 2022. Vol.101. Article number:102499. https://doi.org/10.1016/j.ceca.2021.102499

43. Sharma P., Yi R., Nayak A.P., Wang N., Tang F., Knight M.J., Pan S., Oliver B., Deshpande D.A. Bitter taste receptor agonists mitigate features of allergic asthma in mice // Sci. Rep. 2017. Vol.7. Article number:46166. https://doi.org/10.1038/srep46166

44. Izuhara K., Arima K., Yasunaga S. IL-4 and IL-13: their pathological roles in allergic diseases and their potential in developing new therapies // Curr. Drug Targets Inflamm. Allergy. 2002. Vol.1, Iss.3. P.263–269. https://doi.org/10.2174/1568010023344661

45. Makita K., Mikami Y., Matsuzaki H., Miyashita N., Takeshima H., Noguchi S., Horie M., Urushiyama H., Iikura M., Hojo M., Nagase T., Yamauchi Y. Mechanism of periostin production in human bronchial smooth muscle cells // Int. Arch. Allergy Immunol. 2018. Vol.175, Iss.1–2. P.26–35. https://doi.org/10.1159/000485892

46. Ekoff M., Choi J.H., James A., Dahlén B., Nilsson G., Dahlén S.E. Bitter taste receptor (TAS2R) agonists inhibit IgE-dependent mast cell activation // J. Allergy Clin. Immunol. 2014. Vol.134, Iss.2. P.475–478. https://doi.org/10.1016/j.jaci.2014.02.029

47. Наумов Д.Е., Гассан Д.А., Котова О.О., Шелудько Е.Г., Афанасьева Е.Ю., Конев А.В., Перельман Ю.М. Эффект полиморфизмов гена TAS2R20 на формирование бронхиальной астмы и течение заболевания // Бюллетень физиологии и патологии дыхания. 2024. Вып.94. С.40–50. https://doi.org/10.36604/1998-5029-2024-94-40-50

48. Крапошина А.Ю., Собко Е.А., Демко И.В., Кацер А.Б., Казмерчук О.В., Абрамов Ю.И. Современное представление о бронхиальной астме с фиксированной обструкцией // Терапевтический архив. 2021. Т.93, №3. С.337–342. https://doi.org/10.26442/00403660.2021.03.200661

49. Habib N., Pasha M.A., Tang D.D. Current understanding of asthma pathogenesis and biomarkers // Cells. 2022. Vol.11, Iss.17. Article number:2764. https://doi.org/10.3390/cells11172764

50. Jalševac F., Segú H., Balaguer F., Ocaña T., Moreira R., Abad-Jordà L., Gràcia-Sancho J., Fernández-Iglesias A., Andres-Lacueva C., Martínez-Huélamo M., Beltran-Debon R., Rodríguez-Gallego E., Terra X., Ardévol A., Pinent M. TAS2R5 and TAS2R38 are bitter taste receptors whose colonic expressions could play important roles in age-associated processes // J. Nutr. Biochem. 2025. Vol.140. Article number:109872. https://doi.org/10.1016/j.jnutbio.2025.109872

51. Yang M., Kumar R.K., Hansbro P.M., Foster P.S. Emerging roles of pulmonary macrophages in driving the development of severe asthma // J. Leukoc. Biol. 2012. Vol.91, Iss.4. P.557–569. https://doi.org/10.1189/jlb.0711357

52. Wölfle U., Haarhaus B., Schempp C.M. Amarogentin displays immunomodulatory effects in human mast cells and keratinocytes // Mediators Inflamm. 2015. Vol.2015. Article number:630128. https://doi.org/10.1155/2015/630128

53. Tran H.T.T., Herz C., Ruf P., Stetter R., Lamy E. Human T2R38 bitter taste receptor expression in resting and activated lymphocytes // Front. Immunol. 2018. Vol.9. Article number:2949. https://doi.org/10.3389/fimmu.2018.02949

54. Maurer S., Wabnitz G.H., Kahle N.A., Stegmaier S., Prior B., Giese T., Gaida M.M., Samstag Y., Hänsch 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. Vol.6. Article number:369. https://doi.org/10.3389/fimmu.2015.00369

55. Vidaillac C., Chotirmall S.H. Pseudomonas aeruginosa in bronchiectasis: infection, inflammation, and therapies // Expert Rev. Respir. Med. 2021. Vol.15, Iss.5. P.649–662. https://doi.org/10.1080/17476348.2021.1906225

56. Lee R.J., Kofonow J.M., Rosen P.L., Siebert A.P., Chen B., Doghramji L., Xiong G., Adappa N.D., Palmer J.N., Kennedy D.W., Kreindler J.L., Margolskee R.F., Cohen N.A. Bitter and sweet taste receptors regulate human upper respiratory innate immunity // J. Clin. Invest. 2014. Vol.124, Iss.3. P.1393–1405. https://doi.org/10.1172/JCI72094

57. Kobayashi D., Watarai T., Ozawa M., Kanda Y., Saika F., Kiguchi N., Takeuchi A., Ikawa M., Matsuzaki S., Katakai T. Tas2R signaling enhances mouse neutrophil migration via a ROCK-dependent pathway // Front. Immunol. 2022. Vol. 13. Article number:973880. https://doi.org/10.3389/fimmu.2022.973880

58. Aoki M., Takao T., Takao K., Koike F., Suganuma N. Lower expressions of the human bitter taste receptor TAS2R in smokers: reverse transcriptase-polymerase chain reaction analysis // Tob. Induc. Dis. 2014. Vol.12. Article number:12. https://doi.org/10.1186/1617-9625-12-12

59. Tran H.T.T., Stetter R., Herz C., Spöttel J., Krell M., Hanschen F.S., Schreiner M., Rohn S., Behrens M., Lamy E. Allyl isothiocyanate: a TAS2R38 receptor-dependent immune modulator at the interface between personalized medicine and nutrition // Front. Immunol. 2021. Vol.12. Article number:669005. https://doi.org/10.3389/fimmu.2021.669005

60. Jeruzal-Świątecka J., Borkowska E.M., Borkowska M., Pietruszewska W. TAS2R38 bitter taste receptor polymorphisms in patients with chronic rhinosinusitis with nasal polyps: preliminary data in Polish population // Biomedicines. 2024. Vol.12, Iss.1. Article number:168. https://doi.org/10.3390/biomedicines12010168

61. Calancie L., Keyserling T.C., Smith Taillie L., Robasky K., Patterson C., Ammerman A.S., Schisler J.C. TAS2R38 predisposition to bitter taste associated with differential changes in vegetable intake in response to a community-based dietary intervention // G3 (Bethesda). 2018. Vol.8, Iss.6. P.2107–2119. https://doi.org/10.1534/g3.118.300547

62. Shore S.A. Obesity, airway hyperresponsiveness, and inflammation // J. Appl. Physiol. 2010. Vol.108, Iss.3. P.735–743. https://doi.org/10.1152/japplphysiol.00749.2009

63. Cancello R., Micheletto G., Meta D., Lavagno R., Bevilacqua E., Panizzo V., Invitti C. Expanding the role of bitter taste receptor in extra oral tissues: TAS2R38 is expressed in human adipocytes // Adipocyte. 2020. Vol.9, Iss.1. P.7–15. https://doi.org/10.1080/21623945.2019.1709253

64. Liszt K.I., Wang Q., Farhadipour M., Segers A., Thijs T., Nys L., Deleus E., Tack J., Depoortere I. Human intestinal bitter taste receptors regulate innate immune responses and metabolic regulators in obesity // J. Clin. Invest. 2022. Vol.132, Iss.3. Article number:e144828. https://doi.org/10.1172/JCI144828

65. Foschino Barbaro M.P., Costa V.R., Resta O., Prato R., Spanevello A., Palladino G.P., Martinelli D., Carpagnano G.E. Menopausal asthma: a new biological phenotype? // Allergy. 2010. Vol.65, Iss.10. P.1306–1312. https://doi.org/10.1111/j.1398-9995.2009.02314.x

66. Trivedi S., Deering-Rice C.E., Aamodt S.E., Huecksteadt T.P., Myers E.J., Sanders K.A., Paine R. III, Warren K.J. Progesterone amplifies allergic inflammation and airway pathology in association with higher lung ILC2 responses // Am. J. Physiol. Lung Cell. Mol. Physiol. 2024. Vol.327, Iss.1. P.L65–L78. https://doi.org/10.1152/ajplung.00207.2023

67. Yung J.A., Fuseini H., Newcomb D.C. Hormones, sex, and asthma // Ann. Allergy Asthma Immunol. 2018. Vol.120, Iss.5. P.488–494. https://doi.org/10.1016/j.anai.2018.01.016

68. Lossow K., Hübner S., Roudnitzky N., Slack J.P., Pollastro F., Behrens M., Meyerhof W. Comprehensive analysis of mouse bitter taste receptors reveals different molecular receptive ranges for orthologous receptors in mice and humans // J. Biol. Chem. 2016. Vol.291, Iss.29. P.15358–15377. https://doi.org/10.1074/jbc.M116.718544

69. Ziegler F., Steuer A., Di Pizio A., Behrens M. Physiological activation of human and mouse bitter taste receptors by bile acids // Commun. Biol. 2023. Vol.6, Iss.1. Article number:612. https://doi.org/10.1038/s42003-023-04971-3

70. Jiang J., Liu S., Qi L., Wei Q., Shi F. Activation of ovarian taste receptors inhibits progesterone production potentially via NO/cGMP and apoptotic signaling // Endocrinology. 2021. Vol.162, Iss.3. Article number:bqaa240. https://doi.org/10.1210/endocr/bqaa240

71. Ni K., Che B., Gu R., Wang C., Xu H., Li H., Cen S., Lu o M., Deng L. BitterDB database analysis plus cell stiffness screening identify flufenamic acid as the most potent TAS2R14-based relaxant of airway smooth muscle cells for therapeutic bronchodilation. // Theranostics. 2024. Vol.14, Iss.4 P.1744–1763. https://doi.org/10.7150/thno.92492

72. Sun S., Yang Y., Xiong R., Ni Y., Ma X., Hou M., Chen L., Xu Z., Chen L, Ji M. Oral berberine ameliorates high-fat diet-induced obesity by activating TAS2Rs in tuft and endocrine cells in the gut // Life Sci. 2022. Vol.311, Pt A. Article number:121141. https://doi.org/10.1016/j.lfs.2022.121141

73. Medapati M.R., Singh N., Bhagirath A.Y., Duan K., Triggs-Raine B., Batista E.L. Jr., Chelikani P. Bitter taste receptor T2R14 detects quorum-sensing molecules from cariogenic Streptococcus mutans and mediates innate immune responses in gingival epithelial cells // FASEB J. 2021. Vol.35, Iss.3. Article number:e21375. https://doi.org/10.1096/fj.202000208R

74. Miller Z.A., Mueller A., Kim T.B., Jolivert J.F., Ma R.Z., Muthuswami S., Park A., McMahon D.B., Nead K.T., Carey R.M., Lee R.J. Lidocaine induces apoptosis in head and neck squamous cell carcinoma through activation of bitter taste receptor T2R14 // Cell Rep. 2023. Vol.42, Iss.12. Article number:113437. https://doi.org/10.1016/j.celrep.2023.113437

75. Waterloo L., Hübner H., Fierro F., Pfeiffer T., Brox R., Löber S., Weikert D., Niv M.Y., Gmeiner P. Discovery of 2-aminopyrimidines as potent agonists for the bitter taste receptor TAS2R14 // J. Med. Chem. 2023. Vol.66, Iss.5. P.3499–3521. https://doi.org/10.1021/acs.jmedchem.2c01997

76. Rajagopal S., Shenoy S.K. GPCR desensitization: acute and prolonged phases // Cell. Signal. 2018. Vol.41. P.9–16. http s://doi.org/10.1016/j.cellsig.2017.01.024