ASSOCIATION OF PLASMA LEVELS OF THE TAS2R5 ECTOPIC TASTE RECEPTOR WITH CLINICAL AND FUNCTIONAL CHARACTERISTICS OF BRONCHIAL ASTHMA

  • M.A. Nyoma First Saint-Petersburg State Medical University named after I.P. Pavlov. Leo Tolstoy str., 6–8. Saint Petersburg, Russia, 197022
  • V.N. Mineev First Saint-Petersburg State Medical University named after I.P. Pavlov. Leo Tolstoy str., 6–8. Saint Petersburg, Russia, 197022 https://orcid.org/0000-0003-0352-8137
  • R.G. Murkina First Saint-Petersburg State Medical University named after I.P. Pavlov. Leo Tolstoy str., 6–8. Saint Petersburg, Russia, 197022
  • V.V. Sadovaya First Saint-Petersburg State Medical University named after I.P. Pavlov. Leo Tolstoy str., 6–8. Saint Petersburg, Russia, 197022
Keywords:
бронхиальная астма эктопические вкусовые рецепторы к горькому вкусу TAS2R5 TAS2R31 растворимые рецепторы bronchial asthma ectopic taste receptors for bitter taste TAS2R5 TAS2R31 soluble receptors

Abstract

Introduction. Evidence has accumulated on the role of so-called ectopic taste receptors, located outside the canonical localization, in particular to bitter taste (TAS2R), in the regulation of cellular functions in bronchial asthma (BA). The TAS2R5 receptor subtype is considered one of the dominant subtypes mediating bronchodilation. The aim of the study was to analyze the association of plasma levels of TAS2R5 taste receptor with clinical and functional characteristics of different variants of BA. Materials and methods. Eight practically healthy individuals, 39 patients with allergic BA (ABA) and 19 patients with non-allergic BA (NABA) were examined. The level of TAS2R5 expression in serum was determined by enzyme immunoassay in paired samples by spectrophotometry at a wavelength of 450 nm. Results. Levels of receptors to bitter taste TAS2R5 in blood plasma in different variants of BA differ significantly. In NABA this level is significantly higher than in ABA. The factor analysis revealed 3 factors revealing, in general, a positive relationship between the components of plasma levels of TAS2R5 receptor and the components characterizing the non-allergic variant of BA. Correlation analysis revealed a negative association of plasma levels of TAS2R5 with the Tiffeneau index. Discussion. The data obtained that plasma levels of TAS2R5 receptor have a negative correlation dependence on the index characterizing bronchial obstruction in BA are comparable with the results of the study of TAS2R31 receptor. A similar negative correlation between soluble receptors (TAS2R5 and TAS2R31) and bronchial obstruction suggests that they have the same pathogenetic mechanism in bronchial asthma — binding of the ligand to the corresponding soluble receptor and preventing the availability of ligands for contact with membrane receptors. Conclusions. A negative correlation was found between TAS2R5 and an indicator that identifies bronchial obstruction in bronchial asthma (Tiffeneau index). Factor analysis revealed a positive relationship between the TAS2R5 component and components of the non-allergic variant of bronchial asthma and concomitant diabetes mellitus.

References

Минеев В.Н., Нёма М.А., Трофимов В.И. Эктопические вкусовые рецепторы TAS2R31 в сыворотке крови при различных вариантах бронхиальной астмы. Тихоокеанский медицинский журнал. 2021;1:68–71. DOI: 10.34215/16091175-2021-1-68-71.

Сорокина Л.Н., Иванов В.А., Минеев В.Н., Лим В.В., Трофимов В.И. Особенности цитокинового спектра у больных неаллергической бронхиальной астмой в сочетании с сопутствующим сахарным диабетом 2 типа. Медицинская иммунология. 2017;19(3):313–318. DOI: 10.15789/1563-0625-2017-3-313-318.

Минеев В.Н. Эктопические обонятельные рецепторы в респираторной системе. Пульмонология. 2019;29(6):734–738. DOI: 10.18093/0869-0189-2019-29-6-734-738.

Минеев В.Н., Кузикова А.А., Нёма М.А. Вкусовые рецепторы к горькому вкусу при бронхиальной астме. Медицинский академический журнал, 2017;17(2):105–110.

Grassin-Delyle S., Naline E., Devillier P. Taste receptors in asthma. Curr Opin Allergy Clin Immunol. 2015;15(1):63–69. DOI:10.1097/ACI.0000000000000137.

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;134(2):475–478. DOI: 10.1016/j.jaci.2014.02.029.

Liggett S.B. Bitter taste receptors on airway smooth muscle as targets for novel bronchodilators. Expert Opin Ther Targets. 2013;17(6):721–731. DOI: 10.1517/14728222.2013.782395.

Yoon S.Y., Shin E.S., Park S.Y., Kim S., Kwon H.S., Cho Y.S., Moon H.B., Kim T.B. Association between Polymorphisms in Bitter Taste Receptor Genes and Clinical Features in Korean Asthmatics. Respiration. 2016;91(2):141–50. DOI: 10.1159/000443796.

Минеев В.Н., Трофимов В.И., Нёма М.А., Кузикова А.А. Вкусовые рецепторы к горькому вкусу сыворотки крови при бронхиальной астме (гипотеза). Пульмонология. 2017;27(5):567–572. DOI: 10.18093/0869-0189-2017-27-5-567-572.

Kato E., Oshima S. Association of Bitter Taste Receptors with Obesity and Diabetes and Their Role in Related Tissues. Receptors. 2023;2(4):251–263. DOI: 10.3390/receptors2040017.

Park J., Kim K.S., Kim K.H., Lee I.S., Jeong H.S., Kim Y., Jang H.J. GLP-1 secretion is stimulated by 1.10-phenanthroline via colocalized T2R5 signal transduction in human enteroendocrine L cell. Biochem Biophys Res Commun. 2015;468(1-2):306–311. DOI: 10.1016/j.bbrc.2015.

Kim D., An S.S., Lam H., Leahy J.W., Liggett S.B. Identification and Characterization of Novel Bronchodilator Agonists Acting at Human Airway Smooth Muscle Cell TAS2R5. ACS Pharmacol Transl Sci. 2020;3(6):1069–1075. DOI: 10.1021/acsptsci.0c00127.

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;42(1):65–78. DOI: 10.1183/09031936.00077712.

Иванов В., Рубеко Е., Сорокина Л., Минеев В., Быст­рова А., Трофимов В. Бронхиальная астма в сочетании с сахарным диабетом типа 2: клинико-патогенетические особенности. Врач. 2016;7:36–38.

Иванов В.А., Сорокина Л.Н., Минеев В.Н., Шес­такова Н.Э., Быстрова А.А., Трофимов В.И. Сочетание бронхиальной астмы и сахарного диабета: синергизм или антагонизм? Пульмонология. 2014;6:103–107. DOI: 10.18093/0869-0189-2014-0-6-103-107.

Donath M.Y., Shoelson S.E. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11(2):98–107. DOI: 10.1038/nri2925.

Kempuraj D., Caraffa A., Ronconi G., Lessiani G., Conti P. Are mast cells important in diabetes? Pol J Pathol. 2016;67(3):199–206. DOI: 10.5114/pjp.2016.63770.

Shah H., Eisenbarth S., Tormey C.A., Siddon A.J. Behind the scenes with basophils: an emerging therapeutic target. Immunother Adv. 2021;1(1):ltab008. DOI: 10.1093/immadv/ltab008.

Deshpande D.A., Wang W.C., McIlmoyle E.L., Ro­binett K.S., Schillinger R.M., An S.S., Sham J.S., Liggett S.B. Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nat Med. 2010;16(11):1299–304. DOI: 10.1038/nm.2237.

Levine S.J. Molecular mechanisms of soluble cytokine receptor generation. J Biol Chem. 2008;283(21):14177–81. DOI: 10.1074/jbc.R700052200.

Kefaloyianni E. Soluble forms of cytokine and growth factor receptors: mechanisms of generation and modes of action in the regulation of local and systemic inflammation. FEBS Lett. 2022;596(5):589–606. DOI: 10.1002/1873-3468.14305.

Grau-Bové C., Grau-Bové X., Terra X., Garcia-Vall­ve S., Rodríguez-Gallego E., Beltran-Debón R., Blay M.T., Ardévol A., Pinent M. Functional and genomic comparative study of the bitter taste receptor family TAS2R: Insight into the role of human TAS2R5. FASEB J. 2022;36:e22175. DOI: 10.1096/fj.202101128RR.

Nayak A.P., Shah S.D., Michael J.V., Deshpan­de D.A. Bitter Taste Receptors for Asthma Therapeutics. Front Physiol. 2019;10:884. DOI: 10.3389/fphys.2019.00884.