Skip to main content
SpringerLink
Log in

Octarphin, a nonopioid peptide of opioid origin

  • Review Papers Minireview
  • Published:
Russian Journal of Bioorganic Chemistry Aims and scope Submit manuscript

Abstract

The data on the properties and the mechanism of action of the peptide octarphin (TPLVTLFK, fragment 12–19 of ß-endorphin), a selective agonist of the nonopioid (insensitive to the opioid antagonist naloxone) β-endorphin receptor detected on cells of the immune (peritoneal macrophages, T and β lymphocytes of the spleen and blood), endocrine (adrenal cortex, pituitary), and cardiovascular systems (cardiomyocytes) have been analyzed and systematized. When binding to the receptor, octarphin increases the mitogen- induced proliferation of T and B lymphocytes of human and mouse in vitro, activates murine peritoneal mac-rophages in vitro and in vivo, stimulates the growth of human T-lymphoblast cell lines Jurkat and MT-4, inhibits the activity of adenylate cyclase of rat adrenal cortex membranes, and suppresses the secretion of glucocorticoids from the adrenal gland to the blood. In the concentration range of 1–1000 nM, the peptide increases the activity of inducible NO synthase (iNOS) and the content of NO and cGMP in lipopolysaccharide-activated murine peritoneal macrophages. Taking into account that NO acts as a primary activator of soluble guanylate cyclase (sGC), it can be assumed that the activating effect of octarphin on macrophages is accomplished in the following way: an increase in iNOS expression → an increase in NO production → an increase in sGC activity → an increase in the intracellular cGMP level.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ACTH:

corticotropin

cAMP:

cyclic 3',5'-adenosine monophosphate

cGMP:

cyclic 3',5'-guanosine monophosphate

CRH:

corticotropin-releasing hormone

NOS:

nitric oxide synthase

iNOS:

inducible NO synthase

LPS:

lipopolysaccharide

nNOS:

neuronal NO synthase

POMC:

proopiomelanocortin

sGC:

soluble guanylate cyclase

EMI:

experimental myocardial infarction

References

  1. Crine, P., Gossard, F., Seidah, N.G., Blanchette, L., Lis, M., and Chretien, M., Proc. Natl. Acad. Sci. U.S.A., 1979, vol. 76, pp. 5085–5089.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Li, Ch., Cell, 1982, vol. 31, pp. 504–505.

    Article  CAS  PubMed  Google Scholar 

  3. Hazum, E., Chang, K.J., and Cuatrecasas, P., Science, 1979, vol. 205, pp. 1033–1035.

    Article  CAS  PubMed  Google Scholar 

  4. Kovalitskaya, Yu.A., Sadovnikov, V.B., Kolobov, A.A., Zolotarev, Yu.A., Yurovskii, V.V., Lipkin, V.M., and Navolotskaya, E.V., Russ. J. Bioorg. Chem., 2008, vol. 34, pp. 24–29.

    Article  CAS  Google Scholar 

  5. Navolotskaya, E.V., Kovalitskaya, Ya., Zolotarev, Ya., and Sadovnikov, V.B., J. Peptide Sci., 2008, vol. 14, pp. 1121–1128.

    Article  CAS  Google Scholar 

  6. Roberts, J.L., Seeburg, P.H., Shine, J., Herbert, E., Baxter, J.D., and Goodman, H.M., Proc. Natl. Acad. Sci. U.S.A., 1979, vol. 76, pp. 2153–2157.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Zav’yalov, V.P., Zaitseva, O.R., Navolotskaya, E.V., Abramov, V.M., Volodina, E.Yu., and Mitin, Y.V., Immunol. Lett., 1996, vol. 49, pp. 21–26.

    Article  PubMed  Google Scholar 

  8. Julliard, J.H., Shibasaki, T., Ling, N., and Guilemin, R., Science, 1980, vol. 208, pp. 183–185.

    Article  CAS  PubMed  Google Scholar 

  9. Houck, J.C., Kimball, C., Chang, C., Pedigo, N.W., and Yamamura, H.I., Science, 1980, vol. 207, pp. 78–80.

    Article  CAS  PubMed  Google Scholar 

  10. Navolotskaya, E.V., Malkova, N.V., Lepikhova, T.N., Krasnova, S.B., Zargarova, T.A., Zav’yalov, V.P., and Lipkin, V.M., Russ. J. Bioorg. Chem., 2001, vol. 27, pp. 359–363.

    Article  Google Scholar 

  11. Navolotskaya, E.V., Zargarova, T.A., Malkova, N.V., Lepikhova, T.N., Zav’yalov, V.P., and Lipkin, V.M., Peptides, 2001, vol. 22, pp. 2009–2013.

    Article  CAS  PubMed  Google Scholar 

  12. Navolotskaya, E.V., Malkova, N.V., Zargarova, T.A., Krasnova, S.B., and Lipkin, V.M., Biochemistry (Moscow), 2002, vol. 67, pp. 357–363.

    Article  CAS  Google Scholar 

  13. Navolotskaya, E.V., Zargarova, T.A., Malkova, N.V., Krasnova, S.B., Zav’yalov, V.P., and Lipkin, V.M., Biochem. Biophys. Res. Commun., 2002, vol. 292, pp. 799–804.

    Article  CAS  PubMed  Google Scholar 

  14. 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., Biochemistry (Moscow), 2003, vol. 68, pp. 34–41.

    Article  CAS  Google Scholar 

  15. 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., Biochem. Biophys. Res. Commun., 2003, vol. 303, pp. 1065–1072.

    Article  CAS  PubMed  Google Scholar 

  16. Navolotskaya, E.V., Zargarova, T.A., Malkova, N.V., Krasnova, S.B., Zav’yalov, V.P., and Lipkin, V.M., Peptides, 2002, vol. 23, pp. 1115–1119.

    Article  CAS  PubMed  Google Scholar 

  17. 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., Rus. J. Immunol., 2003, vol. 8, pp. 31–36.

    CAS  Google Scholar 

  18. Navolotskaya, E.V., Kovalitskaya, Yu.A., Zolotarev, Yu.A., Kolobov, A.A., Kampe- Nemm, E.A., Malkova, N.V., Yurovskii, V.V., and Lipkin, V.M., Biochemistry (Moscow), 2004, vol. 69, pp. 394–400.

    Article  CAS  Google Scholar 

  19. Malkova, N.V., Krasnova, S.B., Navolotskaya, E.V., Zargarova, T.A., and Prasolov, V.S., Rus. J. Immunol., 2002, vol. 7, pp. 231–237.

    Google Scholar 

  20. Navolotskaya, E.V., Kovalitskaya, E.V., Zolotaarev, Yu.A., Kudryashova, N.Yu., Goncharenko, E.N., Kolobov, A.A., Kampe- Nemm, E.A., Malkova, N.V., Yurovskii, V.V., and Lipkin, V.M., Biochemistry (Moscow), 2004, vol. 69, pp. 870–875.

    Article  CAS  Google Scholar 

  21. Kovalitskaya, Yu.A., Nekrasova, Yu.N., Sadovnikov, V.B., Zolotarev, Yu.A., and Navolotskaya, E.V., Biochemistry (Moscow), 2011, vol. 76, pp. 596–604.

    Article  CAS  Google Scholar 

  22. Nekrasova, Yu.N. and Navolotskaya, E.V., Biochemistry (Moscow), Suppl. Series A: Membr. Cell Biol., 2012, vol. 6, pp. 82–91.

    Article  Google Scholar 

  23. Nekrasova, Yu.N., Zolotarev, Yu.A., and Navolotskaya, E.V., Biokhimiya, 2013, vol. 78, pp. 407–412.

    Google Scholar 

  24. Nekrasova, Yu.N. and Navolotskaya, E.V., J. Peptide Sci, 2013, vol. 19, pp. 499–503.

    Article  CAS  Google Scholar 

  25. Nekrasova, Yu.N., Zolotarev, Yu.A., and Navolotskaya, E.V., Biochemistry (Moscow), 2012, vol. 77, pp. 1693–1698.

    Google Scholar 

  26. Nekrasova, Yu.N., Zolotarev, Yu.A., and Navolotskaya, E.V., Regul. Peptides, 2013, vol. 183, pp. 23–26.

    Article  CAS  Google Scholar 

  27. Nekrasova, Y.N., Sadovnikov, V.B., Zolotarev, Ya., and Navolotskaya, E.V., J. Peptide Sci, 2010, vol. 16, pp. 263–268.

    CAS  Google Scholar 

  28. Nekrasova, Yu.N., Zolotarev, Yu.A., and Navolotskaya, E.V., Biochemistry (Moscow), 2011, vol. 76, pp. 1337–1341.

    Article  CAS  Google Scholar 

  29. Nekrasova, Y.N., Zolotarev, Ya., and Navolotskaya, E.V., J. Peptide Sci., 2012, vol. 18, pp. 83–87.

    Article  CAS  Google Scholar 

  30. Sadovnikov, V.B. and Navolotskaya, E.V., J. Peptide Sci., 2014, vol. 20, pp. 212–215.

    Article  CAS  Google Scholar 

  31. Nathan, C. and Xie, Q.W., Cell, 1994, vol. 78, pp. 915–918.

    Article  CAS  PubMed  Google Scholar 

  32. James, S.L. and Hibbs, J.B., Parasitol. Today, 1990, vol. 6, pp. 303–305.

    Article  CAS  PubMed  Google Scholar 

  33. Drapier, J.C., Pathol. Biol., 1997, vol. 45, pp. 110–114.

    CAS  PubMed  Google Scholar 

  34. Alam, M.S., Akaike, T., Okamoto, S., Kubota, T., Yoshitake, J., Sawa, T., Miyamoto, Y., Tamura, F., and Maeda, H., Infect. Immun., 2002, vol. 70, pp. 3130–3142.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Abbas, K., Breton, J., Planson, A.G., Bouton, C., Bignon, J., Seguin, C., Riquier, S., Toledano, M.B., and Drapier, J.C., Free Radic. Biol. Med., 2011, vol. 51, pp. 107–114.

    Article  CAS  PubMed  Google Scholar 

  36. Förstermann, U. and Sessa, W.C., Eur. Heart J., 2012, vol. 33, pp. 829–837.

    Article  PubMed Central  PubMed  Google Scholar 

  37. MacMicking, J., Xie, Q.W., and Nathan, C., Annu. Rev. Immunol., 1997, vol. 15, pp. 323–350.

    Article  CAS  PubMed  Google Scholar 

  38. Nathan, C.F. and Hibbs, J.B., Curr. Opin. Immunol., 1991, vol. 3, pp. 65–70.

    Article  CAS  PubMed  Google Scholar 

  39. Okamoto, T., Khan, S., Oyama, K., Fujii, S., Sawa, T., Akaike, T., J. Clin. Biochem. Nutr., 2010, vol. 46, pp. 14–19.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Saura, M., Zaragoza, C., Bao, C., McMillan, A., and Lowenstein, C.J., J. Mol. Biol., 1999, vol. 289, pp. 459–471.

    Article  CAS  PubMed  Google Scholar 

  41. Feelish, M. and Noaclk, E.A., Eur. J. Pharmacol., 1987, vol. 139, pp. 19–30.

    Article  Google Scholar 

  42. Derbyshire, E.R. and Marletta, M.A., Annu. Rev. Biochem., 2012, vol. 81, pp. 533–559.

    Article  CAS  PubMed  Google Scholar 

  43. Murad, F., J. Clin. Invest., 1986, vol. 78, pp. 1–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Bredt, D.S., Hwang, P.M., and Snyder, Sh., Nature, 1990, vol. 347, pp. 768–770.

    Article  CAS  PubMed  Google Scholar 

  45. Dallman, M.F., Akana, S.F., Cascio, C.S., Darlington, D.N., Jacobson, L., and Levin, N., Recent Prog. Horm. Res., 1987, vol. 43, pp. 113–173.

    CAS  PubMed  Google Scholar 

  46. Vale, W., Spiess, J., Rivier, C., and Rivierm, J., Science, 1981, vol. 213, pp. 1394–1397.

    Article  CAS  PubMed  Google Scholar 

  47. Wang, T.Y., Chen, X.Q., Du, J.Z., Xu, N.Y., Wei, C.B., and Vale, W.W., Neuroscience, 2004, vol. 128, pp. 111–119.

    Article  CAS  PubMed  Google Scholar 

  48. Antoni, F.A., Endocr. Rev., 1986, vol. 7, pp. 351–378.

    Article  CAS  PubMed  Google Scholar 

  49. Grahame-Smith, D.G., Butcher, R.W., Ney, R.J., and Sutherland, E.W., J. Biol. Chem., 1967, vol. 242, pp. 5535–5541.

    CAS  PubMed  Google Scholar 

  50. Beuschlein, F., Fassnacht, M., Klink, A., Allolio, B., and Reincke, M., Eur. J. Endocrinol., 2001, vol. 144, pp. 199–206.

    Article  CAS  PubMed  Google Scholar 

  51. Clark, A.J.L., Noon, L., Swords, F.M., Hunyady, L., and King, P., Ann. NY Acad. Sci., 2003, vol. 994, pp. 111–117.

    Article  CAS  PubMed  Google Scholar 

  52. Keller-Wood, M.E. and Dallman, M.F., Endocr. Rev., 1984, vol. 5, pp. 1–24.

    Article  CAS  PubMed  Google Scholar 

  53. Dallman, M.F., Akana, S.F., Jacobson, L., Levin, N., Cascio, C.S., and Shinsako, J., Ann. N. Y. Acad. Sci., 1987, vol. 512, pp. 402–414.

    Article  CAS  PubMed  Google Scholar 

  54. Riad, M., Mogos, M., Thangathurai, D., and Lumb, P.D., Curr. Opin. Crit. Care, 2002, vol. 8, pp. 281–284.

    Article  PubMed  Google Scholar 

  55. Grahame-Smith, D.G., Butcher, R.W., Ney, R.J., and Sutherland, E.W., J. Biol. Chem., 1967, vol. 242, pp. 5535–5541.

    CAS  PubMed  Google Scholar 

  56. Szalay, K.S., J. Steroid Biochem. Mol. Biol., 1993, vol. 45, pp. 141–146.

    Article  CAS  PubMed  Google Scholar 

  57. Kapas, S., Purbrick, A., and Hinson, J.P., J. Endocrinol., 1995, vol. 144, pp. 503–510.

    Article  CAS  PubMed  Google Scholar 

  58. Nekrasova, Yu.N., Biological properties of the synthetic peptide octarphin, Cand. Sci. (Biol.) Dissertation, Moscow: Inst. Biokhim. im. A.N. Bakha, 2013.

    Google Scholar 

  59. Burbach, J.P.H., Loeber, J.G., Verhoef, J., Wiegant, V.M., de Kloet, E.R., and de Wied, D., Nature, 1980, vol. 283, pp. 96–97.

    Article  CAS  PubMed  Google Scholar 

  60. Allen, R.G., Peng, B., Pellegrino, M.J., Miller, E.D., Grandy, D.K., Lundblad, J.R., Washburn, C.L., and Pintar, J.E., J. Neurosci., 2001, vol. 21, pp. 5864–5870.

    CAS  PubMed  Google Scholar 

  61. Miller, R., Aaron, W., Toneff, T., Vishnuvardhan, D., Beinfeld, M.C., and Hook, V.Y., J. Neurochem., vol. 86, pp. 556–563.

  62. Reed, B., Bidlack, J.M., Chait, B.T., and Kreek, M.J., J. Neuroendocrinol., 2008, vol. 20, pp. 606–616.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Sarada, B., Thiele, D., Dang, T., Safavi, A., Hersh, L.B., and Cottam, G.L., J. Leukocyte Biol., 1997, vol. 62, pp. 753–760.

    CAS  PubMed  Google Scholar 

  64. Sandin, J., Nylander, I., and Silberring, J., Regul. Peptides, 1998, vol. 73, pp. 67–72.

    Article  CAS  Google Scholar 

  65. Miller, B.C., Thiele, D., Hersh, L.B., and Cottam, G.L., Immunopharmacology, 1996, vol. 31, pp. 151–161.

    Article  CAS  PubMed  Google Scholar 

  66. Madden, J.J., Whaley, W.L., and Ketelsen, D., J. Neuroimunol., 1998, vol. 83, pp. 57–62.

    Article  CAS  Google Scholar 

  67. Austen, B.M. and Smyth, D.G., Biochem. Soc. Trans., 1977, vol. 5, pp. 1394–1397.

    Article  CAS  PubMed  Google Scholar 

  68. Shoureshi, P., Baron, A., Szynskie, L., and Dores, R.M., Gen. Comp. Endocrinol., 2007, vol. 153, pp. 148–154.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Pushchino Branch, Russian Academy of Sciences, pr. Nauki 6, Pushchino, Moscow, Moscow oblast, 142290, Russia

    E. V. Navolotskaya

Authors
  1. E. V. Navolotskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. V. Navolotskaya.

Additional information

Original Russian Text © E.V. Navolotskaya, 2015, published in Bioorganicheskaya Khimiya, 2015, Vol. 41, No. 5, pp. 524–530.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Navolotskaya, E.V. Octarphin, a nonopioid peptide of opioid origin. Russ J Bioorg Chem 41, 467–473 (2015). https://doi.org/10.1134/S106816201505009X

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S106816201505009X

Keywords

Search

Navigation