Beta-adrenergic and M-cholinergic receptor interactions in the pathogenesis of bronchial obstructive pulmonary diseases

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Abstract

The crosstalk between the beta-2-adrenoceptor and M- cholinoreceptor systems in the airways plays one of the main roles in the pathogenesis of bronchoobstructive diseases. The interaction of M3-cholinergic receptors and beta2-receptors in the lungs can be characterized as functional antagonism. M3 activation can lead to desensitization of beta2 receptors. Beta2 receptors also limit the action of M3 receptors in various ways. In this case, M2 cholinergic receptors act as autoreceptors. On the one hand, they limit bronchoconstriction caused by a change in the conformation of the M3 cholinergic receptor, and, on the other hand, they are able to suppress the excessive bronchorelaxing effect that occurs when a beta2 receptor is activated. The knowledge of the crosstalk mechanisms can help in understanding the pathogenesis of bronchial obstructive diseases, in optimizing the existing treatment regimens for chronic obstructive pulmonary disease (COPD) and bronchial asthma (BA) and will create a new potential in the development of new drug groups

About the authors

Anna V. Eremenko

Research Institute of Pulmonology of the Federal Medical and Biological Agency of Russia

Author for correspondence.
Email: a_nn87@list.ru
ORCID iD: 0000-0001-9333-0022
SPIN-code: 2813-1638
Russian Federation, Moscow

Kirill A. Zykov

Research Institute of Pulmonology of the Federal Medical and Biological Agency of Russia; Moscow State University of Medicine and Dentistry named after A.I. Evdokimov

Email: kirillaz@inbox.ru
SPIN-code: 6269-7990

MD, PhD, Professor

Russian Federation, Moscow

References

  1. Nelson HS, Weiss ST, Bleecker ER, et al. The salmeterol multicenter asthma research trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129(1):15–26. doi: 10.1378/chest.129.1.15.
  2. Global Strategy for Asthma Management and Prevention. 2020. Available from: www.ginasthma.org.
  3. Global Strategy for the Diagnosis, Management, and Prevention of COPD Revised. 2020. Available from: www.goldcopd.com.
  4. Profita M, Bonanno A, Siena L, et al. M Acetylcholine mediates the release of IL-8 in human bronchial epithelial cells by a NFkB/ERK-dependent mechanism. Eur J Pharmacol. 2008;582(1-3):145–153. doi: 10.1016/j.ejphar.2007.12.029.
  5. Hallsworth MP, Twort CH, Lee TH, Hirst SJ. Beta(2)-adrenoceptor agonists inhibit release of eosinophil-activating cytokines from human airway smooth muscle cells. Br J Pharmacol. 2001;132(3):729–741. doi: 10.1038/sj.bjp.0703866.
  6. Gosens R, Zaagsma J, Meurs H, Halayko A. Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir Res. 2006;7(1):73–76. doi: 10.1186/1465-9921-7-73.
  7. Gosens R, Rieks D, Meurs H, et al. Muscarinic M3 receptor stimulation increases cigarette smoke-induced IL-8 secretion by human airway smooth muscle cells. Eur Respir J. 2009;34(6):1436–1443. doi: 10.1183/09031936.00045209.
  8. Matthiesen S, Bahulayan A, Kempkens S, et al Muscarinic receptors mediate stimulation of human lung fibroblast proliferation. Am J Respir Cell Mol Biol. 2006;35(6):621–627. doi: 10.1165/rcmb.2005-0343RC.
  9. Sato E, Koyama S, Okubo Y, et al. Acetylcholine stimulates alveolar macrophages to release inflammatory cell chemotactic activity. Am J Physiol Lung Cell Mol Physiol. 1998;274(6):L970–L979. doi: 10.1152/ajplung.1998.274.6.L970.
  10. Costello RW, Jacoby DB, Fryer AD. Review Pulmonary neuronal M2-receptor function in asthma and animal models of hyperreactivity. Thorax. 1998;53(7):613–615. doi: 10.1136/thx.53.7.613.
  11. Tobin AB, Nahorski SJ. Rapid agonist-mediated phosphorylation of M3- receptors revealed by immunoprecipitation. Biol Chem. 1993;268(13):9817–9822.
  12. Zieba BJ, Artamonov MV, Jin L, et al. The cAMP-responsive Rap1 guanine nucleotide exchange factor, Epac, induces smooth muscle relaxation by down-regulation of RhoA activity. Biol Chem. 2011;286(19):16681–16692. doi: 10.1074/jbc.M110.205062.
  13. Boterman M, Elzinga CR, Wagemakers D, et al Potentiation of beta-adrenoceptor function in bovine tracheal smooth muscle by inhibition of PKC. Eur J Pharmacol. 2005:516(1):85–92. doi: 10.1016/j.ejphar.2005.04.029.
  14. Boterman M, Smits SR, Meurs H, Zaagsma J. Protein kinase C potentiates homologous desensitization of the B2AR in bovine tracheal smooth muscle. Eur J Pharmacol. 2006;529(1-3):151–156. doi: 10.1016/j.ejphar.2005.10.064.
  15. Walker JK, Peppel K, Lefkowitz RJ, et al. Altered airway and cardiac responses in mice lacking GRK. Am J Physiol. 1999;276(4):R1214–1221 doi: 10.1152/ajpregu.1999.276.4.R1214.
  16. Fernandes LB, Fryer AD, Hirshman CA. M2-receptors inhibit isoproterenol-induced relaxation of canine airway smooth muscle. Pharmacol Exp Ther. 1992;262(1):119–126.
  17. Roscioni SS, Maarsingh H, Elzinga CR, et al. Epac as a novel effector of airway smooth muscle relaxation. J Cell Mol Med. 2011;15(7):1551–1563. doi: 10.1111/j.1582-4934.2010.01150.x.
  18. Walker JK, Gainetdinov RR, Feldman DS, et al. G protein-coupled receptor kinase 5 regulates airway responses induced by muscarinic receptor activation. Am J Physiol Lung Cell Mol Physiol. 2004;286(2):312–319. doi: 10.1152/ajplung.00255.2003.
  19. Billington CK, Hall IP, Mundell SJ, et al. Inflammatory and contractile agents sensitize specific adenylyl cyclase isoforms in human airway smooth muscle. Am J Respir Cell Mol Biol. 1999;21(5):597–606. doi: 10.1165/ajrcmb.21.5.3759.
  20. Lamyel F, Warnken-Uhlich M, Seemann WK, et al. The β2-subtype of adrenoceptors mediates inhibition of pro-fibrotic events in human lung fibroblasts. Arch Pharmacol. 2011;384(2):133–145. doi: 10.1007/s00210-011-0655-5.

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2. Fig.: 1. The mechanism of contraction of smooth muscles of the bronchi, realized through the M3-cholinergic receptor

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3. Fig. 2. Interaction of beta2-adrenergic receptors, M2- and M3-cholinergic receptors

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Copyright (c) 2020 Eremenko A.V., Zykov K.A.

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