Immunostimulating effect of the synthetic peptide octarphin corresponding to β-endorphin fragment 12–19
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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 wordsβ-endorphin naloxone peptides receptors immune system
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cytopathic effect of bacteria
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- 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
- 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.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
- 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.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
- 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
- 25.Uchitel, I. Ya. (1978) Macrophages in Immunity [in Russian], Meditsina, Moscow, pp. 168–180.Google Scholar
- 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
- 28.Freidlin, I. S. (1984) Mononuclear Phagocyte System [in Russian], Meditsina, Moscow.Google Scholar