Ukr.Biochem.J. 2013; Volume 85, Issue 6, Nov-Dec, pp. 134-143


Nicotinic acetylcholine receptors: specific antibodies and functions in humoral immunity

M. V. Skok, L. M. Koval, O. Yu. Lykhmus, O. M. Kalashnyk,
G. L. Gergalova, S. V. Komisarenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels initially discovered in muscles and neurons and further found in many non-excitable cells. The present review summarizes the results of studies performed in the Department of Molecular Immunology during the last decade and concerning the structure and functions of nAChRs in B lymphocytes and in mitochondria, as well as the role of nAChR-specific antibodies in the develop­ment of neurodegenerative disorders like Alzheimer disease.

Keywords: , , , ,


  1. Bamel K, Gupta SC, Gupta R. Acetylcholine causes rooting in leaf explants of in vitro raised tomato (Lycopersicon esculentum Miller) seedlings. Life Sci. 2007 May 30;80(24-25):2393-6. PubMed, CrossRef
  2. Kawashima K, Fujii T. Basic and clinical aspects of non-neuronal acetylcholine: overview of non-neuronal cholinergic systems and their biological significance. J Pharmacol Sci. 2008 Feb;106(2):167-73. Review. PubMed, CrossRef
  3. Kummer W, Lips KS, Pfeil U. The epithelial cholinergic system of the airways. Histochem Cell Biol. 2008 Aug;130(2):219-34. Review. PubMed, PubMedCentral, CrossRef
  4. Bocquet N, Prado de Carvalho L, Cartaud J, Neyton J, Le Poupon C, Taly A, Grutter T, Changeux JP, Corringer PJ. A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family. Nature. 2007 Jan 4;445(7123):116-9. PubMed, CrossRef
  5. Changeux JP. The nicotinic acetylcholine receptor: the founding father of the pentameric ligand-gated ion channel superfamily. J Biol Chem. 2012 Nov 23;287(48):40207-15. Review. PubMed, PubMedCentral, CrossRef
  6. Albuquerque EX, Pereira EF, Alkondon M, Rogers SW. Mammalian nicotinic acetylcholine receptors: from structure to function. Physiol Rev. 2009 Jan;89(1):73-120. Review. PubMed, PubMedCentral, CrossRef
  7. Parada E, Egea J, Romero A, del Barrio L, García AG, López MG. Poststress treatment with PNU282987 can rescue SH-SY5Y cells undergoing apoptosis via α7 nicotinic receptors linked to a Jak2/Akt/HO-1 signaling pathway. Free Radic Biol Med. 2010 Dec 1;49(11):1815-21. PubMed, CrossRef
  8. Chernyavsky AI, Arredondo J, Marubio LM, Grando SA. Differential regulation of keratinocyte chemokinesis and chemotaxis through distinct nicotinic receptor subtypes. J Cell Sci. 2004 Nov 1;117(Pt 23):5665-79. PubMed, CrossRef
  9. Arias HR, Richards VE, Ng D, Ghafoori ME, Le V, Mousa SA. Role of non-neuronal nicotinic acetylcholine receptors in angiogenesis. Int J Biochem Cell Biol. 2009 Jul;41(7):1441-51. Review. PubMed, CrossRef
  10. Filippini P, Cesario A, Fini M, Locatelli F, Rutella S. The Yin and Yang of non-neuronal α7-nicotinic receptors in inflammation and autoimmunity. Curr Drug Targets. 2012 May;13(5):644-55. Review. PubMed, CrossRef
  11. Lindstrom JM. Acetylcholine receptors and myasthenia. Muscle Nerve. 2000 Apr;23(4):453-77. Review. PubMed, CrossRef
  12. Wakkach A, Guyon T, Bruand C, Tzartos S, Cohen-Kaminsky S, Berrih-Aknin S. Expression of acetylcholine receptor genes in human thymic epithelial cells: implications for myasthenia gravis. J Immunol. 1996 Oct 15;157(8):3752-60. PubMed
  13. Holt PG, Keast D. Environmentally induced changes in immunological function: acute and chronic effects of inhalation of tobacco smoke and other atmospheric contaminants in man and experimental animals. Bacteriol Rev. 1977 Mar;41(1):205-16. PubMed, PubMedCentral
  14. Skok MV, Voitenko LP, Voitenko SV, Lykhmus EY, Kalashnik EN, Litvin TI, Tzartos SJ, Skok VI. Alpha subunit composition of nicotinic acetylcholine receptors in the rat autonomic ganglia neurons as determined with subunit-specific anti-alpha(181-192) peptide antibodies. Neuroscience. 1999;93(4):1427-36. PubMed, CrossRef
  15. Koval OM, Voitenko LP, Skok MV, Lykhmus EY, Tsetlin VI, Zhmak MN, Skok VI. The beta-subunit composition of nicotinic acetylcholine receptors in the neurons of the guinea pig inferior mesenteric ganglion. Neurosci Lett. 2004 Jul 22;365(2):143-6. PubMed, CrossRef
  16. Shelukhina IV, Kryukova EV, Skok MV, Lykhmus EY, Zhmak MN, Mordvintsev DY, Kasheverov IE, Tsetlin VI. Analysis of specificity of antibodies against synthetic fragments of different neuronal nicotinic acetylcholine receptor subunits. Biochemistry (Mosc). 2006 Jul;71(7):749-58. PubMed, CrossRef
  17. Skok M, Lykhmus E, Bobrovnik S, Tzartos S, Tsouloufis T, Vanderesse R, Coutrot F, Thong Cung M, Marraud M, Krikorian D, Sakarellos-Daitsiotis M. Structure of epitopes recognized by the antibodies to alpha(181-192) peptides of neuronal nicotinic acetylcholine receptors: extrapolation to the structure of acetylcholine-binding domain. J Neuroimmunol. 2001 Dec 3;121(1-2):59-66. PubMed, CrossRef
  18. Koval L, Lykhmus O, Zhmak M, Khruschov A, Tsetlin V, Magrini E, Viola A, Chernyavsky A, Qian J, Grando S, Komisarenko S, Skok M. Differential involvement of α4β2, α7 and α9α10 nicotinic acetylcholine receptors in B lymphocyte activation in vitro. Int J Biochem Cell Biol. 2011 Apr;43(4):516-24. PubMed, CrossRef
  19. Skok M, Grailhe R, Agenes F, Changeux JP. The role of nicotinic acetylcholine receptors in lymphocyte development. J Neuroimmunol. 2006 Feb;171(1-2):86-98. PubMed, CrossRef
  20. Koval’ LM, Romaniuk SI, Kolybo DV, Skok MV, Komisarenko SV. The role of nicotine in regulation of lymphocyte proliferation. Ukr Biokhim Zhurn. 2005 Mar-Apr;77(2):105-11. Ukrainian. PubMed
  21. Skok MV, Kalashnik EN, Koval LN, Tsetlin VI, Utkin YN, Changeux JP, Grailhe R. Functional nicotinic acetylcholine receptors are expressed in B lymphocyte-derived cell lines. Mol Pharmacol. 2003 Oct;64(4):885-9. PubMed, CrossRef
  22. Skok M, Grailhe R, Changeux JP. Nicotinic receptors regulate B lymphocyte activation and immune response. Eur J Pharmacol. 2005 Jul 11;517(3):246-51. PubMed, CrossRef
  23. Koval LM, Yu Lykhmus O, Omelchenko DM, Komisarenko SV, Skok MV. The role of alpha7 nicotinic acetylcholine receptors in B lymphocyte activation. Ukr Biokhim Zhurn. 2009 Jul-Aug;81(4):5-11. PubMed
  24. Koval LM, Zverkova AS, Grailhe R, Utkin YN, Tsetlin VI, Komisarenko SV, Skok MV. Nicotinic acetylcholine receptors alpha4beta2 and alpha7 regulate myelo- and erythropoiesis within the bone marrow. Int J Biochem Cell Biol. 2008;40(5):980-90. PubMed, CrossRef
  25. Omelchenko DM, Kalashnik OM, Koval LM, Skok MV, Komisarenko SV. Analysis of signaling pathways activated by nicotinic acetylcholine receptors in B-lymphocyte-derived cells. Ukr Biokhim Zhurn. 2009 Jan-Feb;81(1):59-66. PubMed
  26. Parada E, Egea J, Romero A, del Barrio L, García AG, López MG. Poststress treatment with PNU282987 can rescue SH-SY5Y cells undergoing apoptosis via α7 nicotinic receptors linked to a Jak2/Akt/HO-1 signaling pathway. Free Radic Biol Med. 2010 Dec 1;49(11):1815-21.  PubMed, CrossRef
  27. Cormier A, Morin C, Zini R, Tillement JP, Lagrue G. In vitro effects of nicotine on mitochondrial respiration and superoxide anion generation. Brain Res. 2001 May 4;900(1):72-9. PubMed, CrossRef
  28. Li Y, Meyer EM, Walker DW, Millard WJ, He YJ, King MA. Alpha7 nicotinic receptor activation inhibits ethanol-induced mitochondrial dysfunction, cytochrome c release and neurotoxicity in primary rat hippocampal neuronal cultures. J Neurochem. 2002 May;81(4):853-8. PubMed, CrossRef
  29. Gergalova G, Lykhmus O, Kalashnyk O, Koval L, Chernyshov V, Kryukova E, Tsetlin V, Komisarenko S, Skok M. Mitochondria express α7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria. PLoS One. 2012;7(2):e31361. PubMed, PubMedCentral, CrossRef
  30. Kalashnyk OM, Gergalova GL, Komisarenko SV, Skok MV. Intracellular localization of nicotinic acetylcholine receptors in human cell lines. Life Sci. 2012 Nov 27;91(21-22):1033-7. PubMed, CrossRef
  31. Winston N, Vernino S. Recent advances in autoimmune autonomic ganglionopathy. Curr Opin Neurol. 2010 Oct;23(5):514-8. Review. PubMed, CrossRef
  32. Hellström-Lindahl E, Mousavi M, Zhang X, Ravid R, Nordberg A. Regional distribution of nicotinic receptor subunit mRNAs in human brain: comparison between Alzheimer and normal brain. Mol Brain Res. 1999 Mar 20;66(1-2):94-103. PubMed, CrossRef
  33. Lykhmus O, Koval L, Pavlovych S, Zouridakis M, Zisimopoulou P, Tzartos S, Tsetlin V, Volpina O, Cloëz-Tayarani I, Komisarenko S, Skok M. Functional effects of antibodies against non-neuronal nicotinic acetylcholine receptors. Immunol Lett. 2010 Jan 18;128(1):68-73. PubMed, CrossRef
  34. Lykhmus O, Koval L, Skok M, Zouridakis M, Zisimopoulou P, Tzartos S, Tsetlin V, Granon S, Changeux JP, Komisarenko S, Cloëz-Tayarani I. Antibodies against extracellular domains of α4 and α7 subunits alter the levels of nicotinic receptors in the mouse brain and affect memory: possible relevance to Alzheimer’s pathology. J Alzheimers Dis. 2011;24(4):693-704.  PubMed
  35. Koval L, Lykhmus O, Kalashnyk O, Bachinskaya N, Kravtsova G, Soldatkina M, Zouridakis M, Stergiou C, Tzartos S, Tsetlin V, Komisarenko S, Skok M. The presence and origin of autoantibodies against α4 and α7 nicotinic acetylcholine receptors in the human blood: possible relevance to Alzheimer’s pathology.  J Alzheimers Dis. 2011;25(4):747-61.  PubMed

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