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Sympathetic Innervation and Endogenous Catecholamines in Neuromuscular Preparations of Muscles with Different Functional Profiles

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Abstract

Influence of the sympathetic nervous system on the work of skeletal muscles contractile apparatus is now beyond doubt. However, until recently there was no evidence that the endings of sympathetic nerves can be located in close proximity to the neuromuscular synapses, and there is also no reliable data on how much endogenous adrenaline and noradrenaline can be contained near the synaptic contact in skeletal muscles. In this research, using fluorescent analysis, immunohistochemical and enzyme immunoassays the isolated neuromuscular preparations of three skeletal muscles of different functional profiles and containing different types of muscle fibers were examined. Close contact between the sympathetic and motor cholinergic nerve endings and the presence of tyrosine hydroxylase in this area were demonstrated. Concentrations of endogenous adrenaline and noradrenaline in the solution perfusing the neuromuscular preparation were determined under different modes of its functioning. The effects of α and β adrenoreceptor blockers on the processes of acetylcholine quantal secretion from the motor nerve endings were compared. The data obtained provide evidence for the presence of endogenous catecholamines in the neuromuscular junction region and their role in modulation of the synaptic function.

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Abbreviations

AD:

adrenaline

ADR:

adrenoreceptors

NA:

noradrenaline

NMP:

neuromuscular preparation

References

  1. Corkill, A. B., and Tiegs, O. W. (1933) The effect of sympathetic nerve stimulation on the power of contraction of skeletal muscle, J. Physiol., 78, 161-185, https://doi.org/10.1113/jphysiol.1933.sp002995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Brown, G. L., Bülbring, E., and Burns, B. D. (1948) The action of adrenaline on mammalian skeletal muscle, J. Physiol., 107, 115-128, https://doi.org/10.1113/jphysiol.1948.sp004255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Steiner, J. L., Johnson, B. R., Hickner, R. C., Ormsbee, M. J., Williamson, D. L., and Gordon, B. S. (2021) Adrenal stress hormone action in skeletal muscle during exercise training: An old dog with new tricks?, Acta Physiol. (Oxf), 231, e13522, https://doi.org/10.1111/apha.13522.

    Article  CAS  PubMed  Google Scholar 

  4. Kvetnansky, R., Lu, X., and Ziegler, M. G. (2013) Stress-triggered changes in peripheral catecholaminergic systems, Adv. Pharmacol., 68, 359-397, https://doi.org/10.1016/B978-0-12-411512-5.00017-8.

    Article  CAS  PubMed  Google Scholar 

  5. Tank, A. W., and Lee Wong, D. (2015) Peripheral and central effects of circulating catecholamines, Compr. Physiol., 5, 1-15, https://doi.org/10.1002/cphy.c140007.

    Article  PubMed  Google Scholar 

  6. Zouhal, H., Jacob, C., Delamarche, P., and Gratas-Delamarche, A. (2008) Catecholamines and the effects of exercise, training and gender, Sports Med., 38, 401-423, https://doi.org/10.2165/00007256-200838050-00004.

    Article  PubMed  Google Scholar 

  7. Andersson, D. C., Betzenhauser, M. J., Reiken, S., Umanskaya, A., Shiomi, T., and Marks, A. R. (2012) Stress-induced increase in skeletal muscle force requires protein kinase A phosphorylation of the ryanodine receptor, J. Physiol., 590, 6381-6387, https://doi.org/10.1113/jphysiol.2012.237925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Khan, M. M., Lustrino, D., Silveira, W. A., Wild, F., Straka, T., Issop, Y., O'Connor, E., Cox, D., Reischl, M., Marquardt, T., Labeit, D., Labeit, S., Benoit, E., Molgó, J., Lochmüller, H., Witzemann, V., Kettelhut, I. C., Navegantes, L. C., Pozzan, T., and Rudolf, R. (2016) Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease, Proc. Natl. Acad. Sci. USA, 113, 746-750, https://doi.org/10.1073/pnas.1524272113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Straka, T., Vita, V., Prokshi, K., Hörner, S. J., Khan, M. M., Pirazzini, M., Williams, M. P. I., Hafner, M., Zaglia, T., and Rudolf, R. (2018) Postnatal development and distribution of sympathetic innervation in mouse skeletal muscle, Int. J. Mol. Sci., 19, 1935, https://doi.org/10.3390/ijms19071935.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kim, J., Grotegut, C. A., Wisler, J. W., Li, T., Mao, L., Chen, M., Chen, W., Rosenberg, P. B., Rockman, H. A., and Lefkowitz, R. J. (2018) β-arrestin 1 regulates β2-adrenergic receptor-mediated skeletal muscle hypertrophy and contractility, Skelet. Muscle, 8, 39, https://doi.org/10.1186/s13395-018-0184-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Williams, R. S., Caron, M. G., and Daniel, K. (1984) Skeletal muscle beta-adrenergic receptors: variations due to fiber type and training, Am. J. Physiol., 246, 160-167, https://doi.org/10.1152/ajpendo.1984.246.2.E160.

    Article  Google Scholar 

  12. Hinkle, R. T., Hodge, K. M. B., Cody, D. B., Sheldon, R. J., Kobilka, B. K., and Isfort, R. J. (2002) Skeletal muscle hypertrophy and anti-atrophy effects of clenbuterol are mediated by the beta2-adrenergic receptor, Muscle Nerve, 25, 729-734, https://doi.org/10.1002/mus.10092.

    Article  CAS  PubMed  Google Scholar 

  13. Lynch, G. S., and Ryall, J. G. (2008) Role of beta-adrenoceptor signaling in skeletal muscle: implications for muscle wasting and disease, Physiol. Rev., 88, 729-767, https://doi.org/10.1152/physrev.00028.2007.

    Article  CAS  PubMed  Google Scholar 

  14. Tsentsevitsky, A., Kovyazina, I., and Bukharaeva, E. (2019) Diverse effects of noradrenaline and adrenaline on the quantal secretion of acetylcholine at the mouse neuromuscular junction, Neuroscience, 423, 162-171, https://doi.org/10.1016/j.neuroscience.2019.10.049.

    Article  CAS  PubMed  Google Scholar 

  15. Nagatsu, T., Levitt, M., and Udenfriend, S. (1964) Tyrosine hydroxylase. The initial step in norepinephrine biosynthesis, J. Biol. Chem., 239, 2910-2917, https://doi.org/10.1016/S0021-9258(18)93832-9.

    Article  CAS  PubMed  Google Scholar 

  16. Tsentsevitsky, A., Nurullin, L., Tyapkina, O., and Bukharaeva, E. (2020) Sympathomimetics regulate quantal acetylcholine release at neuromuscular junctions through various types of adrenoreceptors, Mol. Cell. Neurosci., 108, 103550, https://doi.org/10.1016/j.mcn.2020.103550.

    Article  CAS  PubMed  Google Scholar 

  17. Arkhipov, A., Khuzakhmetova, V., Petrov, A. M., and Bukharaeva, E. A. (2022) Catecholamine-dependent hyperpolarization of the junctional membrane via β2-adrenoreceptor/Gi-protein/α2-Na-K-ATPase pathway, Brain Res., 1795, 148072, https://doi.org/10.1016/j.brainres.2022.148072.

    Article  CAS  PubMed  Google Scholar 

  18. Khuzakhmetova, V., and Bukharaeva, E. (2020) Adrenaline facilitates synaptic transmission by synchronizing release of acetylcholine quanta from motor nerve endings, Cell. Mol. Neurobiol., 41, 395-401, https://doi.org/10.1007/s10571-020-00840-3.

    Article  PubMed  Google Scholar 

  19. Anderson, A. J., and Harvey, A. L. (1988) Effects of the facilitatory compounds catechol, guanidine, noradrenaline and phencyclidine on presynaptic currents of mouse motor nerve terminals, Naunyn. Schmiedebergs. Arch. Pharmacol., 338, 133-137, https://doi.org/10.1007/bf00174860.

    Article  CAS  PubMed  Google Scholar 

  20. Bukcharaeva, E. A., Kim, K. C., Moravec, J., Nikolsky, E. E., and Vyskočil, F. (1999) Noradrenaline synchronizes evoked quantal release at frog neuromuscular junctions, J. Physiol., 517, 879-888, https://doi.org/10.1111/j.1469-7793.1999.0879s.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kuba, K. (1970) Effects of catecholamines on the neuromuscular junction in the rat diaphragm, J. Physiol., 211, 551-570, https://doi.org/10.1113/jphysiol.1970.sp009293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kuba, K., and Tomita, T. (1971) Noradrenaline action on nerve terminal in the rat diaphragm, J. Physiol., 217, 19-31, https://doi.org/10.1113/jphysiol.1971.sp009557.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rodrigues, A. Z., Wang, Z. M., Messi, M. L., and Delbono, O. (2019) Sympathomimetics regulate neuromuscular junction transmission through TRPV1, P/Q- and N-type Ca2+ channels, Mol. Cell. Neurosci., 95, 59-70, https://doi.org/10.1016/j.mcn.2019.01.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gubernator, N. G., Zhang, H., Staal, R. G., Mosharov, E. V., Pereira, D. B., Yue, M., Balsanek, V., Vadola, P. A., Mukherjee, B., Edwards, R. H., Sulzer, D., and Sames, D. (2009) Fluorescent false neurotransmitters visualize dopamine release from individual presynaptic terminals, Science, 324, 1441-1444, https://doi.org/10.1126/science.1172278.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Betz, W. J., and Bewick, G. S. (1992) Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction, Science, 255, 200-203, https://doi.org/10.1126/science.1553547.

    Article  CAS  PubMed  Google Scholar 

  26. Reid, B., Slater, C. R., Bewick, G. S. (1999) Synaptic vesicle dynamics in rat fast and slow motor nerve terminals, J. Neurosci., 19, 2511-2521, https://doi.org/10.1523/JNEUROSCI.19-07-02511.1999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Petrov, A., Zakirjanova, G., Kovyazina, I., Tsentsevitsky, A., and Bukharaeva, E. (2022) Adrenergic receptors control frequency-dependent switching of the exocytosis mode between “full-collapse” and “kiss-and-run” in murine motor nerve terminal, Life Sci., 296, 120433, https://doi.org/10.1016/j.lfs.2022.120433.

    Article  CAS  PubMed  Google Scholar 

  28. Murphy, J. F., Davies, D. H., and Smith, C. J. (1992) The development of enzyme-linked immunosorbent assays (ELISA) for the catecholamines adrenalin and noradrenalin, J. Immunol. Meth., 154, 89-98, https://doi.org/10.1016/0022-1759(92)90216-g.

    Article  CAS  Google Scholar 

  29. Slater, C. R. (2015) The functional organization of motor nerve terminals, Prog Neurobiol., 134, 55-103, https://doi.org/10.1016/j.pneurobio.2015.09.004.

    Article  PubMed  Google Scholar 

  30. Westermann, J., Hubl, W., Kaiser, N., and Salewski, L. (2002) Simple, rapid and sensitive determination of epinephrine and norepinephrine in urine and plasma by non-competitive enzyme immunoassay, compared with HPLC method, Clin Lab., 48, 61-71.

    CAS  PubMed  Google Scholar 

  31. Tekin, I., Roskoski, R. Jr., Carkaci-Salli, N., and Vrana, K. E. (2014) Complex molecular regulation of tyrosine hydroxylase, J. Neural. Transm., 121, 1451-1481, https://doi.org/10.1007/s00702-014-1238-7.

    Article  CAS  PubMed  Google Scholar 

  32. Bruhwyler, J., Liégeois, J. F., and Géczy, J. (1997) Pirlindole: a selective reversible inhibitor of monoamine oxidase A. A review of its preclinical properties, Pharmacol. Res., 36, 23-33, https://doi.org/10.1006/phrs.1997.0196.

    Article  CAS  PubMed  Google Scholar 

  33. Peyrin, L., and Dalmaz, Y. (1975) Peripheral secretion and inactivation of catecholamines (adrenaline, noradrenaline, dopamine) [In French], J. Physiol., 70, 353-433.

    CAS  Google Scholar 

  34. Eisenhofer, G., Kopin, I., and Goldstein, D. (2004) Catecholamine metabolism: a contemporary view with implications for physiology and medicine, Pharmacol. Rev., 56, 331-349, https://doi.org/10.1124/pr.56.3.1.

    Article  CAS  PubMed  Google Scholar 

  35. Hjemdahl, P., Daleskog, M., and Kahan, T. (1979) Determination of plasma catecholamines by high performance liquid chromatography with electrochemical detection: comparison with a radioenzymatic method, Life Sci., 25, 131-138, https://doi.org/10.1016/0024-3205(79)90384-9.

    Article  CAS  PubMed  Google Scholar 

  36. Liao, Y. T., Wang, S. M., Wang, J. R., Yu, C. K., and Liu, C. C. (2015) Norepinephrine and epinephrine enhanced the infectivity of enterovirus, PLoS One, 10, e0135154, https://doi.org/10.1371/journal.pone.0135154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Li, J., King, N. C., and Sinoway, L. I. (2005) Interstitial ATP and norepinephrine concentrations in active muscle, Circulation, 111, 2748-2751, https://doi.org/10.1161/CIRCULATIONAHA.104.510669.

    Article  CAS  PubMed  Google Scholar 

  38. Martin, W. H., Murphree, S. S., and Saffitz, J. E. (1989) Beta-adrenergic receptor distribution among muscle fiber types and resistance arterioles of white, red, and intermediate skeletal muscle, Circ. Res., 64, 1096-1105, https://doi.org/10.1161/01.res.64.6.1096.

    Article  CAS  PubMed  Google Scholar 

  39. Dorszewska, J., Prendecki, M., Oczkowska, A., Rozycka, A., Lianeri, M., and Kozubski, W. (2013) Polymorphism of the COMT, MAO, DAT, NET and 5-HTT genes, and biogenic amines in Parkinson’s disease, Curr. Genomics, 14, 518-533, https://doi.org/10.2174/1389202914666131210210241.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Goldstein, D. S. (2020) The “sick-but-not-dead” phenomenon applied to catecholamine deficiency in neurodegenerative diseases, Semin. Neurol., 40, 502-514, https://doi.org/10.1055/s-0040-1713874.

    Article  PubMed  Google Scholar 

  41. Abercrombie, E. D., Keller, R. W. Jr, and Zigmond, M. J. (1988) Characterization of hippocampal norepinephrine release as measured by microdialysis perfusion: pharmacological and behavioral studies, Neuroscience, 27, 897-904, https://doi.org/10.1016/0306-4522(88)90192-3.

    Article  CAS  PubMed  Google Scholar 

  42. Lim, S. P., and Muir, T. C. (1983) Microelectrode recording of the effects of agonists and antagonists on alpha-adrenoceptors on rat somatic nerve terminals, Br. J. Pharmacol., 80, 41-46, https://doi.org/10.1111/j.1476-5381.1983.tb11047.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wang, Z. M., Rodrigues, A. C. Z., Messi, M. L., and Delbono, O. (2020) Aging blunts sympathetic neuron regulation of motoneurons synaptic vesicle release mediated by β1- and α2B-adrenergic receptors in geriatric mice, J. Gerontol. A Biol. Sci. Med. Sci., 75, 1473-1480, https://doi.org/10.1093/gerona/glaa022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rodrigues, A. C. Z., Messi, M. L., Wang, Z. M., Abba, M. C., Pereyra, A., Birbrair, A., Zhang, T., O’Meara, M., Kwan, P., and Lopez, E. I. S. (2019) The sympathetic nervous system regulates and acetylcholine receptor stability, Acta Physiol., 225, 13195, https://doi.org/10.1111/apha.13195.

    Article  CAS  Google Scholar 

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Acknowledgments

The authors express their gratitude to A.M. Petrov for critical review of the manuscript and helpful suggestions.

Funding

This work was financially supported by the Russian Science Foundation (project no. 18-15-0046). ELISA, sample preparation and data analysis were performed by S.A. Dmitrieva and S.G. Vologin with the support from the government assignment for FRC Kazan Scientific Center of the Russian Academy of Sciences.

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Contributions

E.A. Bukharaeva – conceptualization, supervision, methodology, writing, review & editing; S.A. Dmitrieva, S.G. Vologin – enzyme immunoassay; A.N. Tsentsevitzky, A.Yu. Arkhipov, V.F. Khuzakhmetova – preparing and investigation of experimental samples; G.V. Sibgatullina – immunohistochemical analysis.

Corresponding author

Correspondence to Ellya A. Bukharaeva.

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The authors declare no conflict of interest in financial or any other sphere. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Dmitrieva, S.A., Vologin, S.G., Tsentsevitsky, A.N. et al. Sympathetic Innervation and Endogenous Catecholamines in Neuromuscular Preparations of Muscles with Different Functional Profiles. Biochemistry Moscow 88, 364–373 (2023). https://doi.org/10.1134/S0006297923030069

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