UDC

612.112.9.91

DOI

10.37482/2687-1491-Z112

Authors

Inna G. Paturova* ORCID: https://orcid.org/0000-0002-8555-4525
Tat’yana V. Polezhaeva** ORCID: https://orcid.org/0000-0003-4999-3077
Oksana O. Zaytseva** ORCID: https://orcid.org/0000-0001-9427-0420
Ol’ga N. Solomina** ORCID: https://orcid.org/0000-0001-5187-8698
Andrey N. Khudyakov** ORCID: https://orcid.org/0000-0003-3757-8263
Marta I. Sergushkina** ORCID: https://orcid.org/0000-0002-3113-527Х
Viktor I. Tsirkin*** ORCID: https://orcid.org/0000-0003-3467-3919
Svetlana L. Dmitrieva**** ORCID: https://orcid.org/0000-0002-2505-0202
*Kirov State Medical University (Kirov, Russian Federation)
**Federal Research Centre “Komi Science Center of the Ural Branch of the Russian Academy of Sciences” (Syktyvkar, Komi Republic, Russian Federation)
***Kazan State Medical University (Kazan, Republic of Tatarstan, Russian Federation)
****Kirov Regional Clinical Perinatal Centre (Kirov, Russian Federation)
Corresponding author: Inna Paturova, address: ul. K. Marksa 112, Kirov, 610027, Russian Federation; e-mail: paturova_ig@mail.ru

Abstract

The aim of this paper was to determine the effect of the beta3-adrenergic receptor agonist mirabegron on the free-radical activity of venous blood neutrophils in non-pregnant women. Materials and methods. Using the chemiluminescent method (BChL-07 biochemiluminometer), the parameters of the radical response of venous blood neutrophils in 40 non-pregnant women were determined in different phases of the cycle and on the first day after childbirth with additional cell stimulation with latex particles (0.08 μm). When the noise level was automatically subtracted, the following were recorded: maximum intensity of the synthesis of reactive oxygen species, time to reach the maximum of synthesis intensity, and area under the chemiluminogram curve, reflecting the total synthesis of radical particles over the course of 30 min. These parameters were determined before and after an in vitro introduction of the beta -adrenergic receptor agonist mirabegron (10–6 g/l), beta-adrenergic receptor blocker propranolol hydrochloride (10–6 g/l) and agonist against the background of the blocker into the venous blood. Results. Using the Wilcoxon signed-rank test, we showed an increase in the free-radical activity of neutrophils in women in the follicular phase of the menstrual cycle under the influence of mirabegron for all three evaluated parameters. In the luteal phase, mirabegron significantly increased the rate of reaction development and the total synthesis of radical particles, but did not affect the intensity of production of activated oxygen species. However, no effect was observed on the first day after delivery. The possible mechanism of the revealed mirabegron action is discussed in the article. The authors believe that changes in the activity of venous blood neutrophils under the action of mirabegron may be due to changes in the quantity or sensitivity of beta3-adrenergic receptors in different phases of reproduction.

Keywords

mirabegron, beta-adrenergic receptors, respiratory burst of neutrophils, non-pregnant women, phases of the menstrual cycle, new mothers

References

1. Finlin B.S., Memetimin H., Zhu B., Confides A.L., Vekaria H.J., El Khouli R.H., Johnson Z.R., Westgate P.M., Chen J., Morris A.J., Sullivan P.G., Dupont-Versteegden E.E., Kern P.A. The β3-Adrenergic Receptor Agonist Mirabegron Improves Glucose Homeostasis in Obese Humans. J. Clin. Invest., 2020, vol. 130, no. 5, pp. 2319–2331. DOI: 10.1172/JCI134892
2. Cypess A.M., Weiner L.S., Roberts-Toler C., Franquet Elía E., Kessler S.H., Kahn P.A., English J., Chatman K., Trauger S.A., Doria A., Kolodny G.M. Activation of Human Brown Adipose Tissue by a β3-Adrenergic Receptor Agonist. Cell Metab., 2015, vol. 21, no. 1, pp. 33–38. DOI: 10.1016/j.cmet.2014.12.009
3. Bertholet A.M., Kazak L., Chouchani E.T., Bogaczyńska M.G., Paranjpe I., Wainwright G.L., Bétourné A., Kajimura S., Spiegelman B.M., Kirichok Y. Mitochondrial Patch Clamp of Beige Adipocytes Reveals UCP1-Positive and UCP1-Negative Cells Both Exhibiting Futile Creatine Cycling. Cell Metab., 2017, vol. 25, no. 4, pp. 811–822. DOI: 10.1016/j.cmet.2017.03.002
4. MacPherson R.E.K., Dragos S.M., Ramos S., Sutton C., Frendo-Cumbo S., Castellani L., Watt M.J., Perry C.G.R., Mutch D.M., Wright D.C. Reduced ATGL-Mediated Lipolysis Attenuates β-Adrenergic-Induced AMPK Signaling, but Not the Induction of PKA-Targeted Genes, in Adipocytes and Adipose Tissue. Am. J. Physiol. Cell Physiol., 2016, vol. 311, no. 2, pp. C269–C276. DOI: 10.1152/ajpcell.00126.2016
5. Ferrari F., Bock P.M., Motta M.T., Helal L. Biochemical and Molecular Mechanisms of Glucose Uptake Stimulated by Physical Exercise in Insulin Resistance State: Role of Inflammation. Arq. Bras. Cardiol., 2019, vol. 113, no. 6, pp. 1139–1148. DOI: 10.5935/abc.20190224
6. Belge C., Hammond J., Dubois-Deruy E., Manoury B., Hamelet J., Beauloye C., Markl A., Pouleur A.-C., Bertrand L., Esfahani H., Jnaoui K., Götz K.R., Nikolaev V.O., Vanderper A., Herijgers P., Lobysheva I., Iaccarino G., Hilfiker-Kleiner D., Tavernier G., Langin D., Dessy C., Balligand J.-L. Enhanced Expression of β3-Adrenoceptors in Cardiac Myocytes Attenuates Neurohormone-Induced Hypertrophic Remodeling Through Nitric Oxide Synthase. Circulation, 2014, vol. 129, no. 4, pp. 451–462. DOI: 10.1161/CIRCULATIONAHA.113.004940
7. Balligand J.-L. Cardiac Salvage by Tweaking with Beta-3-Adrenergic Receptors. Cardiovasc. Res., 2016, vol. 111, no. 2, pp. 128–133. DOI: 10.1093/cvr/cvw056
8. Michel L.Y.M., Balligand J.-L. New and Emerging Therapies and Targets: Beta-3 Agonists. Handb. Exp. Pharmacol., 2017, vol. 243, pp. 205–223. DOI: 10.1007/164_2016_88
9. Wang B., Xu M., Li W., Li X., Zheng Q., Niu X. Aerobic Exercise Protects Against Pressure Overload-Induced Cardiac Dysfunction and Hypertrophy via β3-AR-nNOS-NO Activation. PLoS One, 2017, vol. 12, no. 6. Art. no. e0179648. DOI: 10.1371/journal.pone.0179648
10. Zhang M., Xu Y., Chen J., Qin C., Liu J., Guo D., Wang R., Hu J., Zou Q., Yang J., Wang Z., Niu X. Beta3Adrenergic Receptor Activation Alleviates Cardiac Dysfunction in Cardiac Hypertrophy by Regulating Oxidative Stress. Oxid. Med. Cell. Longev., 2021, vol. 2021. Art. no. 3417242. DOI: 10.1155/2021/3417242
11. Bubb K.J., Ravindran D., Cartland S.P., Finemore M., Clayton Z.E., Tsang M., Tang O., Kavurma M.M., Patel S., Figtree G.A. β3 Adrenergic Receptor Stimulation Promotes Reperfusion in Ischemic Limbs in a Murine Diabetic Model. Front. Pharmacol., 2021, vol. 12. Art. no. 666334. DOI: 10.3389/fphar.2021.666334
12. Wang J., Zhou Z., Cui Y., Li Y., Yuan H., Gao Z., Zhu Z., Wu J. Meta-Analysis of the Efficacy and Safety of Mirabegron and Solifenacin Monotherapy for Overactive Bladder. Neurourol. Urodyn., 2019, vol. 38, no. 1, pp. 22–30. DOI: 10.1002/nau.23863
13. Calvani M., Dabraio A., Bruno G., De Gregorio V., Coronnello M., Bogani C., Ciullini S., Marca G., Vignoli M., Chiarugi P., Nardi M., Vannucchi A.M., Filippi L., Favre C. β3-Adrenoreceptor Blockade Reduces Hypoxic Myeloid Leukemic Cells Survival and Chemoresistance. Int. J. Mol. Sci., 2020, vol. 21, no. 12. Art. no. 4210. DOI: 10.3390/ ijms21124210
14. Procino G., Carmosino M., Milano S., Dal Monte M., Schena G., Mastrodonato M., Gerbino A., Bagnoli P., Svelto M. β3 Adrenergic Receptor in the Kidney May Be a New Player in Sympathetic Regulation of Renal Function. Kidney Int., 2016, vol. 90, no. 3, pp. 555–567. DOI: 10.1016/j.kint.2016.03.020
15. Yu X.-Y., Lin S.-G., Wang X.-M., Liu Y., Zhang B., Lin Q.-X., Yang M., Zhou S.-F. Evidence for Coexistence of Three β-Adrenoceptor Subtypes in Human Peripheral Lymphocytes. Clin. Pharmacol. Ther., 2007, vol. 81, no. 5, pp. 654–658. DOI: 10.1038/sj.clpt.6100154
16. Hadi T., Douhard R., Dias A.M.M., Wendremaire M., Pezzè M., Bardou M., Sagot P., Garrido C., Lirussi F. Beta3 Adrenergic Receptor Stimulation in Human Macrophages Inhibits NADPHoxidase Activity and Induces Catalase Expression via PPARγ Activation. Biochim. Biophys. Acta Mol. Cell Res., 2017, vol. 1864, no. 10, pp. 1769–1784. DOI: 10.1016/j.bbamcr.2017.07.003
17. Takusagawa S., van Lier J.J., Suzuki K., Nagata M., Meijer J., Krauwinkel W., Schaddelee M., Sekiguchi M., Miyashita A., Iwatsubo T., van Gelderen M., Usui T. Absorption, Metabolism and Excretion of [(14)C]Mirabegron (YM178), a Potent and Selective β3-Adrenoceptor Agonist, After Oral Administration to Healthy Male Volunteers. Drug Metab. Dispos., 2012, vol. 40, no. 4, pp. 815–824. DOI: 10.1124/dmd.111.043588
18. Panasenko L.M., Krasnova E.I., Efremov A.V. Klinicheskoe znachenie khemilyuminestsentnogo otveta leykotsitov krovi pri koklyushe [Chemoluminescence of Solid Blood Leukocytes in Children Suffering from Whooping Cough and Its Clinical Significance]. Byuleten’ Sibirskogo otdeleniya RAMN, 2005, vol. 25, no. 3, pp. 44–47.
19. Quinn M.T., Gauss K.A. Structure and Regulation of the Neutrophil Respiratory Burst Oxidase: Comparison with Nonphagocyte Oxidases. J. Leukoc. Biol., 2004, vol. 76, no. 4, pp. 760–781. DOI: 10.1189/jlb.0404216
20. Kanashiro A., Hiroki C.H., da Fonseca D.M., Birbrair A., Ferreira R.G., Bassi G.S., Fonseca M.D., Kusuda R., Cebinelli G.C.M., da Silva K.P., Wanderley C.W., Menezes G.B., Alves-Fiho J.C., Oliveira A.G., Cunha T.M., Pupo A.S., Ulloa L., Cunha F.Q. The Role of Neutrophils in Neuro-Immune Modulation. Pharmacol. Res., 2020, vol. 151. Art. no. 104580. DOI: 10.1016/j.phrs.2019.104580
21. Marino F., Scanzano A., Pulze L., Pinoli M., Rasini E., Luini A., Bombelli R., Legnaro M., de Eguileor M., Cosentino M. β2-Adrenoceptors Inhibit Neutrophil Extracellular Traps in Human Polymorphonuclear Leukocytes. J. Leukoc. Biol., 2018, vol. 104, no. 3, pp. 603–614. DOI: 10.1002/JLB.3A1017-398RR
22. Polezhaeva T.V., Paturova I.G., Zaytseva O.O., Solomina O.N., Khudyakov A.N., Sergushkina M.I., Dmitrieva S.L., Tsirkin V.I. Effect of Beta-Adrenergic Agonist Gynipral on the Radical Activity of Neutrophils in the Blood of Women at Different Stages of Reproduction. J. Med. Biol. Res., 2021, vol. 9, no. 2, pp. 171–181. DOI: 10.37482/2687-1491-Z055
23. Scanzano A., Schembri L., Rasini E., Luini A., Dallatorre J., Legnaro M., Bombelli R., Congiu T., Cosentino M., Marino F. Adrenergic Modulation of Migration, CD11b and CD18 Expression, ROS and Interleukin-8 Production by Human Polymorphonuclear Leukocytes. Inflamm. Res., 2015, vol. 64, no. 2, pp. 127–135. DOI: 10.1007/s00011- 014-0791-8
24. Gibson-Berry K.L., Whitin J.C., Cohen H.J. Modulation of the Respiratory Burst in Human Neutrophils by Isoproterenol and Dibutyryl Cyclic AMP. J. Neuroimmunol., 1993, vol. 43, no. 1-2, pp. 59–68. DOI: 10.1016/0165- 5728(93)90075-a
25. Brunskole Hummel I., Reinartz M.T., Kälble S., Burhenne H., Schwede F., Buschauer A., Seifert R. Dissociations in the Effects of β2-Adrenergic Receptor Agonists on cAMP Formation and Superoxide Production in Human Neutrophils: Support for the Concept of Functional Selectivity. PLoS One, 2013, vol. 8, no. 5. Art. no. e64556. DOI: 10.1371/journal.pone.0064556
26. Motiejunaite J., Amar L., Vidal-Petiot E. Adrenergic Receptors and Cardiovascular Effects of Catecholamines. Ann. Endocrinol. (Paris), 2021, vol. 82, no. 3-4, pp. 193–197.
27. Luppi P., Irwin T.E., Simhan H., DeLoia J.A. CD11b Expression on Circulating Leukocytes Increases in Preparation for Parturition. Am. J. Reprod. Immunol., 2004, vol. 52, no. 5, pp. 323–329. DOI: 10.1111/j.1600- 0897.2004.00229.x
28. Chapple C.R., Cardozo L., Nitti V.W., Siddiqui E., Michel M.C. Mirabegron in Overactive Bladder: A Review of Efficacy, Safety, and Tolerability. Neurourol. Urodyn., 2014, vol. 33, no. 1, pp. 17–30. DOI: 10.1002/nau.22505