Advertisement

Biochemistry (Moscow)

, Volume 76, Issue 5, pp 596–604 | Cite as

Immunostimulating effect of the synthetic peptide octarphin corresponding to β-endorphin fragment 12–19

  • Yu. A. Kovalitskaya
  • Yu. N. Nekrasova
  • V. B. Sadovnikov
  • Yu. A. Zolotarev
  • E. V. NavolotskayaEmail author
Article

Abstract

We have synthesized the peptide TPLVTLFK corresponding to β-endorphin fragment 12–19 (dubbed octarphin) and its analogs (LPLVTLFK, TLLVTLFK, TPLVLLFK, TPLVTLLK, TPLVTLFL). The octarphin peptide was labeled with tritium (specific activity 28 Ci/mol), and its binding to murine peritoneal macrophages was studied. [3H]Octarphin was found to bind to macrophages with high affinity (K d = 2.3 ± 0.2 nM) and specificity. The specific binding of [3H]octarphin was inhibited by unlabeled β-endorphin and the selective agonist of nonopioid β-endorphin receptor synthetic peptide immunorphin (SLTCLVKGFY) (K i = 2.7 ± 0.2 and 2.4 ± 0.2 nM, respectively) and was not inhibited by unlabeled nalox-one, α-endorphin, γ-endorphin, or [Met5]enkephalin (K i > 10 μM). Inhibitory activity of unlabeled octarphin analogs was more than 100 times lower than that of unlabeled octarphin. Octarphin was shown to stimulate activity of murine immuno-competent cells in vitro and in vivo: at concentration of 1–10 nM it enhanced the adhesion and spreading of peritoneal macrophages as well as their ability to digest bacteria of Salmonella typhimurium virulent strain 415 in vitro; the peptide administered intraperitoneally at a dose of 20 μg/animal on day 7, 3, and 1 prior to isolation of cells increased activity of peritoneal macrophages as well as spleen T- and B-lymphocytes.

Key words

β-endorphin naloxone peptides receptors immune system 

Abbreviations

Con A

concanavalin A

CPE

cytopathic effect of bacteria

LPS

lipopolysaccharide

PA

phagocytic activity

PN

phagocytic number

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Li, C. H. (1982) Cell, 31, 504–505.PubMedCrossRefGoogle Scholar
  2. 2.
    Hazum, E., Chang, K. J., and Cuatrecasas, P. (1979) Science, 205, 1033–1035.PubMedCrossRefGoogle Scholar
  3. 3.
    Julliard, J. H., Shibasaki, T., Ling, N., and Guilemin, R. (1980) Science, 208, 183–185.PubMedCrossRefGoogle Scholar
  4. 4.
    Houck, J. C., Kimball, C., Chang, C., Pedigo, N. W., and Yamamura, H. I. (1980) Science, 207, 78–80.PubMedCrossRefGoogle Scholar
  5. 5.
    Zav’yalov, V. P., Zaitseva, O. R., Navolotskaya, E. V., Abramov, V. M., Volodina, E. Yu., and Mitin, Y. V. (1996) Immunol. Lett., 49, 21–26.PubMedCrossRefGoogle Scholar
  6. 6.
    Navolotskaya, E. V., Malkova, N. V., Lepikhova, T. N., Krasnova, S. B., Zargarova, T. A., Zav’yalov, V. P., and Lipkin, V. M. (2001) Bioorg. Khim. (Moscow), 27, 359–363.Google Scholar
  7. 7.
    Navolotskaya, E. V., Zargarova, T. A., Malkova, N. V., Lepikhova, T. N., Zav’yalov, V. P., and Lipkin, V. M. (2001) Peptides, 22, 2009–2013.PubMedCrossRefGoogle Scholar
  8. 8.
    Navolotskaya, E. V., Malkova, N. V., Zargarova, T. A., Krasnova, S. B., and Lipkin, V. M. (2002) Biochemistry (Moscow), 67, 357–363.CrossRefGoogle Scholar
  9. 9.
    Navolotskaya, E. V., Zargarova, T. A., Malkova, N. V., Krasnova, S. B., Zav’yalov, V. P., and Lipkin, V. M. (2002) Biochem. Biophys. Res. Commun., 292, 799–804.PubMedCrossRefGoogle Scholar
  10. 10.
    Navolotskaya, E. V., Kolobov, A. A., Kampe-Nemm, E. A., Zargarova, T. A., Malkova, N. V., Krasnova, S. B., Kovalitskaya, Yu. A., Zav’yalov, V. P., and Lipkin, V. M. (2003) Biochemistry (Moscow), 68, 34–41.CrossRefGoogle Scholar
  11. 11.
    Navolotskaya, E. V., Zargarova, T. A., Malkova, N. V., Zharmukhamedova, T. Yu., Kolobov, A. A., Kampe-Nemm, E. A., Yurovsky, V. V., and Lipkin, V. M. (2003) Biochem. Biophys. Res. Commun., 303, 1065–1072.PubMedCrossRefGoogle Scholar
  12. 12.
    Navolotskaya, E. V., Zargarova, T. A., Malkova, N. V., Krasnova, S. B., Zav’yalov, V. P., and Lipkin, V. M. (2002) Peptides, 23, 1115–1119.PubMedCrossRefGoogle Scholar
  13. 13.
    Krasnova, S. B., Malkova, N. V., Kovalitskaya, Yu. A., Zolotarev, Yu. A., Zargarova, T. A., Kolobov, A. A., Kampe-Nemm, E. A., Navolotskaya, E. V., and Lipkin, V. M. (2003) Rus. J. Immunol., 8, 31–36.Google Scholar
  14. 14.
    Malkova, N. V., Krasnova, S. B., Navolotskaya, E. V., Zargarova, T. A., and Prasolov, V. S. (2002) Rus. J. Immunol., 7, 231–237.Google Scholar
  15. 15.
    Navolotskaya, E. V., Kovalitskaya, Yu. A., 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.CrossRefGoogle Scholar
  16. 16.
    Sakharova, N. Yu., Lepikhova, T. N., Lepikhov, K. A., Malkova, N. V., Navolotskaya, E. V., and Chaylachyan, L. M. (2002) Dokl. Akad. Nauk, 385, 258–261.Google Scholar
  17. 17.
    Kovalitskaya, Yu. A., Smirnov, A. A., Sakharova, N. Yu., Navolotskaya, E. V., and Chaylachyan, L. M. (2005) Dokl. Akad. Nauk, 405, 137–141.Google Scholar
  18. 18.
    Navolotskaya, E. V., Kovalitskaya, Yu. A., Zolotarev, Yu. A., Kolobov, A. A., Kampe-Nemm, E. A., Malkova, N. V., Yurovsky, V. V., and Lipkin, V. M. (2004) Biochemistry (Moscow), 69, 394–400.CrossRefGoogle Scholar
  19. 19.
    Kovalitskaya, Yu. A., Sadovnikov, V. B., Kolobov, A. A., Zolotarev, Yu. A., Yurovsky, V. V., Lipkin, V. M., and Navolotskaya, E. V. (2008) Bioorg. Khim. (Moscow), 34, 36–42.Google Scholar
  20. 20.
    Navolotskaya, E. V., Kovalitskaya, Y. A., Zolotarev, Y. A., and Sadovnikov, V. B. (2008) J. Peptide Sci., 14, 1121–1128.CrossRefGoogle Scholar
  21. 21.
    Schnolzer, M., Alewood, P., Jones, A., Alewood, D., and Kent, S. B. H. (1992) Int. J. Peptide Protein Res., 40, 180–193.CrossRefGoogle Scholar
  22. 22.
    Zolotarev, Yu. A., Dadayan, A. K., Bocharov, E. V., Borisov, Yu. A., Vaskovsky, B. V., Dorokhova, E. M., and Myasoedov, N. F. (2003) Amino Acids, 24, 325–333.PubMedCrossRefGoogle Scholar
  23. 23.
    Pennock, B. E. (1973) Anal. Biochem., 56, 306–309.PubMedCrossRefGoogle Scholar
  24. 24.
    Chang, Y. C., and Prusoff, W. H. (1973) Biochem. Pharmacol., 22, 3099–3108.CrossRefGoogle Scholar
  25. 25.
    Uchitel, I. Ya. (1978) Macrophages in Immunity [in Russian], Meditsina, Moscow, pp. 168–180.Google Scholar
  26. 26.
    Navolotskaya, E. V. (1994) Structural and Functional Studies of α2-Interferon, Interleukin-2 and Human G Immunoglobulin Using Synthetic Peptides: Doctoral dissertation [in Russian], Institute of Immunology, Moscow.Google Scholar
  27. 27.
    Roberts, J. L., Seeburg, P. H., Shine, J., Herbert, E., Baxter, J. D., and Goodman, H. M. (1979) Proc. Natl. Acad. Sci. USA, 76, 2153–2157.PubMedCrossRefGoogle Scholar
  28. 28.
    Freidlin, I. S. (1984) Mononuclear Phagocyte System [in Russian], Meditsina, Moscow.Google Scholar
  29. 29.
    Valdman, A. V., Bondarenko, N. A., Kamysheva, V. A., Kozlovskaya, M. M., and Kalikhevich, V. N. (1982) Byul. Eksp. Biol. Med., 93, 57–60.CrossRefGoogle Scholar
  30. 30.
    Simpkins, C. O., Dickey, C. A., and Fink, M. P. (1984) Life Sci., 34, 2251–2255.PubMedCrossRefGoogle Scholar
  31. 31.
    Ichinose, M., Asai, M., and Sawada, M. (1995) Scand. J. Immunol., 42, 311–316.PubMedCrossRefGoogle Scholar
  32. 32.
    Ortega, E., Forner, M. A., and Barriga, C. (1996) Comp. Immunol. Microbiol. Infect. Dis., 19, 267–274.PubMedCrossRefGoogle Scholar
  33. 33.
    Van den Bergh, P., Rozing, J., and Nagelkerken, L. (1991) Immunology, 72, 537–543.PubMedGoogle Scholar
  34. 34.
    Van den Bergh, P., Rozing, J., and Nagelkerken, L. (1993) Immunology, 79, 18–23.PubMedGoogle Scholar
  35. 35.
    McCain, H. W., Lamster, I. B., Bozzone, J. M., and Grbic, J. T. (1982) Life Sci., 31, 1619–1624.PubMedCrossRefGoogle Scholar
  36. 36.
    Gilmore, W., and Weiner, L. P. (1988) J. Neuroimmunol., 18, 125–138.PubMedCrossRefGoogle Scholar
  37. 37.
    Gilman, S. C., Schwartz, J. M., Milner, R. J., Bloom, F. E., and Feldman, J. D. (1982) Proc. Natl. Acad. Sci. USA, 79, 4226–4230.PubMedCrossRefGoogle Scholar
  38. 38.
    Heijnen, C. J., Croiset, G., Zijlstra, J., and Ballieux, R. E. (1987) Ann. N. Y. Acad. Sci., 496, 161–165.PubMedCrossRefGoogle Scholar
  39. 39.
    Morgan, E. L., Hobbs, M. V., Thoman, M. L., Janda, J., Noonan, D. J., Kadar, J., and Weigle, W. O. (1990) J. Immunol., 144, 2499–2505.PubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  • Yu. A. Kovalitskaya
    • 1
  • Yu. N. Nekrasova
    • 1
  • V. B. Sadovnikov
    • 1
  • Yu. A. Zolotarev
    • 2
  • E. V. Navolotskaya
    • 1
    Email author
  1. 1.Branch of Shemyakin and Ovchinnikov Institute of Bioorganic ChemistryRussian Academy of SciencesPushchino, Moscow RegionRussia
  2. 2.Institute of Molecular GeneticsRussian Academy of SciencesMoscowRussia

Personalised recommendations