Biochemistry (Moscow)

, Volume 76, Issue 3, pp 309–319 | Cite as

Endogenous opioid peptides in regulation of innate immunity cell functions

  • S. V. GeinEmail author
  • T. A. Baeva


Endogenous opioid peptides comprise a group of bioregulatory factors involved in regulation of functional activity of various physiological systems of an organism. One of most important functions of endogenous opioids is their involvement in the interaction between cells of the nervous and immune systems. Summary data on the effects of opioid peptides on regulation of functions of innate immunity cells are presented.

Key words

opioid peptides opiate receptors immunoregulatory effects monocytes/macrophages neutrophils NK cells dendritic cells cAMP 



adenylate cyclase


adrenocorticotropic hormone


protein activator-1


apoptosis-regulating kinase




cyclic adenosine monophosphate


CREB-binding protein


con-canavalin A


(cAMP-response element-binding) transcription factor


corticotropin releasing factor


kinases regulated by extracellular signals


G-protein-coupled receptors


γ interferon


c-Jun N-terminal protein kinases




mitogen-activated protein kinases


melanocyte stimulating hormone γ


nuclear κB factor


natural killers


nociceptin/orphanin FQ


(opioid receptor-like-1) nociceptin receptor


protein kinase A


phorbol myristate acetate




TGF-β-regulated kinase


transforming growth factor β


tumor necrosis factor α


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  1. 1.
    Panerai, A. E., and Sacerdote, P. (1997) Immunol. Today, 18, 317–319.PubMedGoogle Scholar
  2. 2.
    Salzet, M. (2001) Neuroendocrinol. Lett., 22, 467–474.PubMedGoogle Scholar
  3. 3.
    Pepe, S., van den Brink, O., Lakatta, E. G., and Xiao, R. (2004) Cardiovasc. Res., 63, 414–422.PubMedGoogle Scholar
  4. 4.
    Foradori, C. D., Goodman, R. L., and Lehman, M. N. (2005) Neurosciences, 130, 409–418.Google Scholar
  5. 5.
    Owens, P. C., and Smith, R. (1987) Bailliere Clin. Endocrinol. Metab., 1, 415–437.Google Scholar
  6. 6.
    Hale, K. D., Ghanta, V. K., Gauthier, D. K., and Hiramoto, R. N. (2001) Neuroimmunomodulation, 9, 34–40.PubMedGoogle Scholar
  7. 7.
    Peijie, C., Hongwu, L., Fengpeng, X., Jie, R., and Jie, Z. (2003) Life Sci., 72, 2255–2262.PubMedGoogle Scholar
  8. 8.
    Boone, J. B., Jr., and McMillen, D. (1994) Mol. Brain Res., 27, 290–298.PubMedGoogle Scholar
  9. 9.
    Pancheri, P., Zichella, L., Fraioli, F., Carilli, L., Perrone, G., Biondi, M., Fabbri, A., Santoro, A., and Moretti, C. (1985) Psychoneuroendocrinology, 10, 289–301.PubMedGoogle Scholar
  10. 10.
    Nabeshima, T., Katoh, A., Wada, M., and Kameyama, T. (1992) Life Sci., 51, 211–217.PubMedGoogle Scholar
  11. 11.
    O’Connor, T. M., O’Halloran, D. J., and Shanahan, F. (2000) Oxford J. Med., 93, 323–333.Google Scholar
  12. 12.
    Taylor, C. C., Wu, D., Soong, Yi., Yee, J. S., and Szeto, H. H. (1997) J. Pharmacol. Exp. Therap., 280, 416–421.Google Scholar
  13. 13.
    Navolotskaya, E. V., Kovalitskaya, Yu. D., Zolotarev, Yu. A., Kudryashova, N. Yu., Goncharenko, E. N., Kolobov, A. A., Kampe-Nemm, E. A., Malkova, N. V., Yurovsky, V. V., and Lipkin, V. M. (2004) Biochemistry (Moscow), 69, 870–875.Google Scholar
  14. 14.
    Refojo, D., Kovalovsky, D., Young, J. I., Rubinstein, M., Holsboer, F., Reul, J., Low, M. J., and Arzt, E. (2002) J. Neuroimmunol., 131, 126–134.PubMedGoogle Scholar
  15. 15.
    Bilkei-Gorzo, A., Racz, I., Michel, K., Mauer, D., Zimmer, A., Klingmuller, D., and Zimmer, A. (2008) Psychoneuroendocrinology, 33, 425–436.PubMedGoogle Scholar
  16. 16.
    Blalock, J. E. (1999) Ann. N. Y. Acad. Sci., 885, 161–172.PubMedGoogle Scholar
  17. 17.
    Sitte, N., Busch, M., Mousa, S. A., Labuz, D., Rittner, H., Gore, C., Krause, H., Stein, C., and Schafer, M. (2007) J. Neuroimmunol., 183, 133–145.PubMedGoogle Scholar
  18. 18.
    Smith, E. M. (2008) Brain Behav. Immun., 22, 3–14.PubMedGoogle Scholar
  19. 19.
    Manfredi, B., Clementi, E., Sacerdote, P., Bassetti, M., and Panerai, A. E. (1995) Peptides, 16, 699–706.PubMedGoogle Scholar
  20. 20.
    Rittner, H. L., Labuz, D., Richter, J. F., Brack, A., Schafer, M., Stein, C., and Mousa, S. A. (2007) Brain Behav. Immun., 21, 1021–1032.PubMedGoogle Scholar
  21. 21.
    Machelska, H., and Stein, C. (2002) Anesthesia and Analgesia, 95, 1002–1008.PubMedGoogle Scholar
  22. 22.
    Kamphuis, S., Kavelaars, A., Brooimans, R., Kuis, W., Zegers, B. J. M., and Heijnen, C. J. (1997) J. Neuroimmunol., 79, 91–99.PubMedGoogle Scholar
  23. 23.
    Cabot, P. J., Carter, L., Schafer, M., and Stein, C. (2001) Pain, 93, 207–212.PubMedGoogle Scholar
  24. 24.
    Chadzinska, M., Starowicz, K., Scislowska-Czarnecka, A., Bilecki, W., Pierzchala-Koziec, K., Przewlocki, R., Przewlocka, B., and Plytycz, B. (2005) Immunol. Lett., 101, 185–192.PubMedGoogle Scholar
  25. 25.
    Machelska, H. (2007) Neuropeptides, 41, 355–363.PubMedGoogle Scholar
  26. 26.
    Marinova, Z., Vukojevic, V., Surcheva, S., Yakovleva, T., Cebers, G., Pasikova, N., Usynin, I., Hugonin, L., Fang, W., Halberg, M., Hirschberg, D., Bergman, T., Langel, U., Hauser, K. F., Pramanik, A., Aldrich, J. V., Graslunde, A., Terenius, L., and Bakalkin, G. (2005) J. Biol. Chem., 280, 26360–26370.PubMedGoogle Scholar
  27. 27.
    Civelli, O. (2008) in Orphan G Protein-Coupled Receptors and Novel Neuropeptides (Civelli, O., and Zhou, Q.-Y., eds.) Springer, Berlin/Heidelberg, pp. 1–25.Google Scholar
  28. 28.
    Meunier, J.-C., Mollereau, C., Toll, L., Suaudeau, C., Moisand, C., Alvinerie, P., Butour, J.-L., Guillemot, J.-C., Ferrara, P., Monsarrat, B., Mazarguil, H., Vassart, G., Parmentier, M., and Costentin, J. (1995) Nature, 377, 532–535.PubMedGoogle Scholar
  29. 29.
    Reinscheid, R. K., Nothacker, H., Bourson, A., Ardati, A., Henningsen, R. A., Bunzow, J. R., Grandy, D. K., Langen, H., Monsma, F. J., and Civelli, O. (1995) Science, 3, 792–794.Google Scholar
  30. 30.
    Halford, W. P., Gebhardt, B. M., and Carr, D. J. (1995) J. Neuroimmunol., 59, 91–101.PubMedGoogle Scholar
  31. 31.
    Wick, M. J., Minnerath, S. R., Roy, S., Ramakrishnan, S., and Loh, H. H. (1995) Brain Res. Mol. Brain Res., 32, 342–347.PubMedGoogle Scholar
  32. 32.
    Peluso, J., LaForge, K. S., Matthes, H. W., Kreek, M. J., Kieffer, B. L., and Gaveriaux-Ruff, C. (1998) J. Neuroimmunol., 8, 184–192.Google Scholar
  33. 33.
    Fiset, M. E., Gilbert, C., Poubelle, P. E., and Pouliot, M. (2003) Biochemistry, 42, 10498–10505.PubMedGoogle Scholar
  34. 34.
    Arjomand, J., Cole, S., and Evans, C. J. (2002) J. Neuroimmunol., 130, 100–108.PubMedGoogle Scholar
  35. 35.
    Zadina, J. E., Hackler, L., Ge, L.-J., and Kastin, A. J. (1997) Nature (Lond.), 386, 499–502.Google Scholar
  36. 36.
    Jessop, D. S., Richards, L. J., and Harbuz, M. S. (2002) Ann. N. Y. Acad. Sci., 966, 456–463.PubMedGoogle Scholar
  37. 37.
    Mousa, S. A., Machelska, H., Schafer, M., and Stein, C. (2002) J. Neuroimmunol., 126, 5–15.PubMedGoogle Scholar
  38. 38.
    Stein, C., and Lang, L. J. (2009) Curr. Opin. Pharmacol., 9, 3–8.PubMedGoogle Scholar
  39. 39.
    Law, P. Y., and Loh, H. (2006) in Handbook of Neurochemistry and Molecular Neurobiology. Neuroactive Proteins and Peptides (Lajtha, A., ed.) Springer, Germany, pp. 357–389.Google Scholar
  40. 40.
    Kitanaka, N., Kitanaka, J., Hall, F. S., Tatsuta, T., Morita, Y., Takemura, M., Wang, X.-B., and Uhl, G. R. (2008) Synapse, 62, 689–699.PubMedGoogle Scholar
  41. 41.
    Sharp, B. M. (2006) Brain Behav. Immun., 20, 9–14.PubMedGoogle Scholar
  42. 42.
    Naor, Z. (2009) Front. Neuroendocrinol., 30, 10–29.PubMedGoogle Scholar
  43. 43.
    Ram, P. T., and Lyengar, R. (2001) Oncogene, 20, 1601–1606.PubMedGoogle Scholar
  44. 44.
    Ji, R.-R., Gereau, R. W., IV, Malcangio, M., and Strichartz, G. R. (2009) Brain Res. Rev., 60, 135–148.PubMedGoogle Scholar
  45. 45.
    Gao, Y.-J., and Ji, R.-R. (2008) Neurosci. Lett., 437, 180–183.PubMedGoogle Scholar
  46. 46.
    Cuenda, A., and Rousseau, S. (2007) Biochim. Biophys. Acta, 1773, 1358–1375.PubMedGoogle Scholar
  47. 47.
    Raivich, G., and Behrens, A. (2006) Prog. Neurobiol., 78, 347–363.PubMedGoogle Scholar
  48. 48.
    Shahabi, N. A., Daaka, Y., McAllen, K., and Sharp, B. M. (1999) J. Neuroimmunol., 94, 48–57.PubMedGoogle Scholar
  49. 49.
    Shahabi, N. A., McAllen, K., and Sharp, B. M. (2003) Cell. Immunol., 221, 122–127.PubMedGoogle Scholar
  50. 50.
    Zhang, L., Zhao, H., Qiu, Y., Loh, H. H., and Law, P.-Y. (2009) J. Biol. Chem., 23, 1990–2000.Google Scholar
  51. 51.
    Hayakawa, T., Matsuzawa, A., Noguchi, T., Takeda, K., and Ichijo, H. (2006) Microbes Infect., 8, 1098–1107.PubMedGoogle Scholar
  52. 52.
    Elenkov, I. J., Wilder, R. L., Chrousos, G. P., and Vizi, E. S. (2000) Pharmacol. Rev., 52, 595–638.PubMedGoogle Scholar
  53. 53.
    Moscat, J., Diaz-Meco, M. T., and Rennert, P. (2003) EMBO Rep., 4, 31–36.PubMedGoogle Scholar
  54. 54.
    Ichinos, M., Asai, M., and Sawada, M. (1995) Scand. J. Immunol., 42, 311–316.Google Scholar
  55. 55.
    Pasnik, J., Tchorzewski, H., Baj, Z., Luciak, M., and Tchorzewski, M. (1999) Immunol. Lett., 67, 77–83.PubMedGoogle Scholar
  56. 56.
    Plotnikoff, N. P., Faith, R. E., and Murgo, A. J. (1999) Cytokines: Stress and Immunity, CRC Press, Boca Raton, FL.Google Scholar
  57. 57.
    Van den Bergh, P., Rozing, J., and Nagelkerken, L. (1993) Cell Immunol., 149, 180–192.PubMedGoogle Scholar
  58. 58.
    Andjelkov, N., Elvenes, J., Martin, J., and Johansen, O. (2005) Biochem. Biophys. Res. Commun., 333, 1295–1299.PubMedGoogle Scholar
  59. 59.
    Gein, S. V., Gorshkova, K. G., and Tendryakova, S. P. (2009) Neurosci. Behav. Physiol., 39, 591–595.PubMedGoogle Scholar
  60. 60.
    Kovalovsky, D., Pereda, M. P., Stalla, G. K., Holsboer, F., and Arzt, E. (1999) Neuroimmunomodulation, 6, 367–372.PubMedGoogle Scholar
  61. 61.
    Gein, S. V., and Gorshkova, K. G. (2008) Bull. Exp. Biol. Med., 145, 427–430.Google Scholar
  62. 62.
    Straub, R. H., Dorner, M., Riedel, J., Kubitza, M., van Rooijen, N., Lang B., Scholmerich, J., and Falk, W. (1998) Am. J. Physiol., 274, R997–R1003.PubMedGoogle Scholar
  63. 63.
    Manfredi, B., Sacerdote, P., Gaspani, L., Poli, V., and Panerai, A. E. (1998) Brain Behav. Immun., 12, 201–211.PubMedGoogle Scholar
  64. 64.
    Gein, S. V., Gorshkova, K. G., and Tendryakova, S. P. (2007) Bull. Exp. Biol. Med., 143, 175–178.Google Scholar
  65. 65.
    Nandhra, T. S., and Carson, R. J. (2000) Mol. Hum. Reprod., 6, 555–560.PubMedGoogle Scholar
  66. 66.
    Kowalski, J., Gabryel, B., Aabuzek, K., and Herman, Z. S. (2002) Neuropeptides, 3, 401–406.Google Scholar
  67. 67.
    Marotti, T., Burek, B., Rabatic, S., Balog, T., and Hrsak, I. (1994) Immunol. Lett., 40, 43–47.PubMedGoogle Scholar
  68. 68.
    Kowalski, J., Makowiecka, K., Belowski, D., and Herman, Z. S. (2000) Neuropeptides, 34, 187–192.PubMedGoogle Scholar
  69. 69.
    Zhong, F., Li, X.-Y., Yang, S.-L., Stefano G. B., Fimiani, C., and Bilfinger, T. V. (1998) Int. J. Cardiol., 64, S53–S59.PubMedGoogle Scholar
  70. 70.
    Kamphuis, S., Eriksson, F., Kavelaars, A., Zijlstra, J., van de Pol, M., Kuis, W., and Heijnen, G. J. (1998) J. Neuroimmunol., 84, 53–60.PubMedGoogle Scholar
  71. 71.
    Marotti, T., Balog, T., Mauran, R., and Roi, B. (1998) Neuropeptides, 32, 57–62.PubMedGoogle Scholar
  72. 72.
    Ichinose, M., Asai, M., and Sawada, M. (1995) J. Neuroimmunol., 60, 37–43.PubMedGoogle Scholar
  73. 73.
    Van den Bergh, P., Dobber, R., Ramlal, S., Rosing, J., and Nagelkerken, L. (1994) Cell Immunol., 154, 109–122.PubMedGoogle Scholar
  74. 74.
    Bidlack, J. M. (2000) Clin. Diagn. Lab. Immunol., 7, 719–723.PubMedGoogle Scholar
  75. 75.
    Zhao, H., Wu, G. C., and Cao, X. D. (2002) Acta Pharmacol. Sin., 23, 343–348.PubMedGoogle Scholar
  76. 76.
    Goldfarb, Y., Reinscheid, R. K., and Kusnecov, A. W. (2006) J. Neuroimmunol., 176, 76–85.PubMedGoogle Scholar
  77. 77.
    Li, W. Y., Yang, J. J., Zhu, S. H., Liu, H. J., and Xu, J. G. (2008) Curr. Therap. Res., 69, 56–64.Google Scholar
  78. 78.
    Azuma, Y., and Ohura, K. (2002) Scand. J. Immunol., 56, 209–260.Google Scholar
  79. 79.
    Azuma, Y., and Ohura, K. (2002) Inflammation, 26, 223–232.PubMedGoogle Scholar
  80. 80.
    Inui, Y., Azuma, Y., and Ohura, K. (2002) Int. Immunopharmacol., 2, 1133–1142.PubMedGoogle Scholar
  81. 81.
    Menzebach, A., Hirsch, J., Hempelmann, G., and Welters, I. D. (2003) Br. J. Anaesth., 91, 546–550.PubMedGoogle Scholar
  82. 82.
    Seifert, R., Burde, R., and Schultz, G. (1989) Naunyn-Schmiedebergs Arch. Pharmacol., 340, 101–106.PubMedGoogle Scholar
  83. 82.
    Sharp, B. M., Keane, W. F., Suh, H. J., Gekker, G., Tsukayama, D., and Peterson, P. K. (1985) Endocrinology, 117, 793–795.PubMedGoogle Scholar
  84. 83.
    Slaoui-Hasnaoui, A., Guerin, M. C., Le Doucen, C., Loubatiere, J., and Torreilles, J. (1992) Biochem. Pharmacol., 43, 503–506.PubMedGoogle Scholar
  85. 84.
    Pasotti, D., Mazzone, A., Lecchini, S., Frigo, G. M., and Ricevuti, G. (1993) Eur. Rev. Med. Pharmacol. Sci., 15, 71–81.Google Scholar
  86. 85.
    Sulowska, Z., Majewska, E., Krawczyk, K., Klink, M., and Tchorzewski, H. (2002) Mediators Inflammation, 11, 245–250.Google Scholar
  87. 86.
    Serhan, C. N., Fierro, I. M., Chiang, N., and Pouliot, M. (2001) J. Immunol., 166, 3650–3654.PubMedGoogle Scholar
  88. 87.
    Trombella, S., Vergura, R., Falzarano, S., Guerrini, R., Calo, G., and Spisani, S. (2005) Peptides, 26, 1497–1502.PubMedGoogle Scholar
  89. 88.
    Azuma, Y., Wang, P.-L., Shinohara, M., and Ohura, K. (2000) Immunol. Lett., 75, 55–59.PubMedGoogle Scholar
  90. 89.
    Azuma, Y., Ohura, K., Wang, P.-L., and Shinohara, M. (2002) Immunol. Lett., 81, 31–40.PubMedGoogle Scholar
  91. 90.
    Dokur, M., Chen, C. P., Advis, J. P., and Sarkar, D. K. (2005) J. Neuroimmunol., 166, 29–38.PubMedGoogle Scholar
  92. 91.
    Hsueh, C. M., Chen, S., Ghanta, V. K., and Hiramoto, R. N. (1995) Brain Res., 678, 76–82.PubMedGoogle Scholar
  93. 92.
    Jonsdottir, C. H., Johansson, C., Asea, A., Hellstrand, K., Thoren, P., and Hoffmann, P. (1996) Regul. Pept., 62, 113–118.PubMedGoogle Scholar
  94. 93.
    Faith, R. E., Liang, H. J., Murgo, A. J., and Plotnikoff, N. P. (1984) Clin. Immunol. Immunopathol., 31, 412–418.PubMedGoogle Scholar
  95. 94.
    Bajpai, K., Singh, V. K., Agarwal, S. S., Dhawan, V. C., Naqvi, T., Haq, W., and Mathur, K. B. (1995) Int. J. Immunopharmacol., 17, 207–212.PubMedGoogle Scholar
  96. 95.
    Hsueh, C., Hiramoto, R. N., and Ghanta, V. K. (1992) Brain Res., 578, 142–148.PubMedGoogle Scholar
  97. 96.
    Marotti, T., Rabatic, S., and Gabrilovac, J. (1993) Int. J. Immunopharmacol., 15, 919–926.PubMedGoogle Scholar
  98. 97.
    Zalys, R., Zagon, I. S., Bonneau, R. H., Lang, C. M., and McLaughlin, P. J. (2000) Life Sci., 66, 829–834.PubMedGoogle Scholar
  99. 98.
    Gabrilovac, J., Antica, M., and Osmak, M. (1992) Life Sci., 50, 29–37.PubMedGoogle Scholar
  100. 99.
    Oleson, D., Grierson, H., Goldsmith, J., Purtilo, D. T., and Johnson, D. (1989) Clin. Immunol. Immunopathol., 51, 386–395.PubMedGoogle Scholar
  101. 100.
    Carrigan, K. A., Nelson, C. J., and Lysle, D. T. (2000) Psychopharmacology, 151, 299–305.PubMedGoogle Scholar
  102. 101.
    Pruett, S. B. (2003) Pathophysiology, 9, 133–153.PubMedGoogle Scholar
  103. 102.
    Makarenkova, V. P., Esche, C., Kost, N. V., Shurin, G. V., Rabin, B. S., Zozulya, A. A., and Shurin, M. R. (2001) J. Neuroimmunol., 117, 68–77.PubMedGoogle Scholar
  104. 103.
    Kirst, A., Wack, C., Lutz, W. K., Eggert, A., Kampgen, E., and Fischer, W. H. (2002) Immunol. Lett., 84, 41–48.PubMedGoogle Scholar
  105. 104.
    Benard, A., Boue, J., Chapey, E., Jaume, M., Gomes, B., and Dietrich, G. (2008) J. Neuroimmunol., 197, 21–28.PubMedGoogle Scholar
  106. 105.
    Li, C. H., and Chung, D. (1976) Proc. Natl. Acad. Sci. USA, 73, 1145–1148.PubMedGoogle Scholar
  107. 106.
    Zozulya, A. A., and Pshenichkin, S. F. (1990) Advances in Science and Technology. Ser. Immunology [in Russian], Vol. 25, VINITI, Moscow, pp. 48–120.Google Scholar
  108. 107.
    Hackler, L., Zadina, J. E., Ge, L.-J., and Kastin, A. J. (1997) Peptides, 18, 1635–1639.PubMedGoogle Scholar
  109. 108.
    Zadina, J. E., Hackler, L., Ge, L.-J., and Kastin, A. J. (1997) Nature (Lond.), 386, 499–502.Google Scholar
  110. 109.
    Hughes, J., Smith, T. W., Kosterlitz, H. W., Fothergill, L. A., Morgan, G. A., and Morris, H. R. (1975) Nature (Lond.), 258, 577–580.Google Scholar
  111. 110.
    Chavkin, C., James, I. F., and Goldstein, A. (1982) Science (Wash. DC), 215, 413–415.Google Scholar
  112. 111.
    Meunier, J.-C., Mollereau, C., Toll, L., Suaudeau, C., Moisand, C., Alvinerie, P., Butour, J.-L., Guillemot, J.-C., Ferrara, P., Monsarrat, B., Mazarguil, H., Vassart, G., Parmentier, M., and Costentin, G. (1995) Nature (Lond.), 377, 532–535.Google Scholar
  113. 112.
    Reinscheid, R. K., Nothacker, H.-P., Bourson, A., Ardati, A., Henningsen, R. A., Bunzow, J. R., Grandy, D. K., Langen, H., Monsma, F. J., and Civelli, O. (1995) Science (Wash. DC), 270, 792–794.Google Scholar
  114. 113.
    Peluso, J., Gaveriaux-Ruff, C., Matthes, H. W. D., Filliol, D., and Kieffer, B. L. (2001) Brain Res. Bull., 54, 655–660.PubMedGoogle Scholar
  115. 114.
    Hosoi, J., Ozawa, H., and Greinstein, R. D. (1999) Ann. N. Y. Acad. Sci., 885, 405–413.PubMedGoogle Scholar

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© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  1. 1.Institute of Ecology and Genetics of MicroorganismsUral Branch of the Russian Academy of SciencesPermRussia
  2. 2.Perm State UniversityPermRussia

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