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Analgesic activity of dipeptide Tyr-Pro

  • Animal and Human Physiology
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Abstract

The effect of dipeptide Tyr-Pro, present in representatives of most families of opioid peptides, and two its analogs, Tyr-Pro-NH2 and Tyr-Pro-OMe, on analgesic activity was studied in different tests (tail-flick test, tail pinch (Haffner’s) test, formalin test, and acetic acid writing test) describing different organization levels of pain sensitivity. Intraperitoneal administration of the dipeptide decreased the pain threshold in all above-mentioned tests. Coadministration of the dipeptide and naloxone or naloxone methiodide insignificantly decreased the dipeptide analgesic effect in the tail-flick and acetic acid writing tests. Its analogs Tyr-Pro-NH2 and Tyr-Pro-OMe demonstrated a similar analgesic activity in the tail-flick test and a higher activity in the acetic acid writing test. Administration of individual amino acids (Tyr or Pro) or their mixture had no effect on the pain threshold.

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References

  • Alfeeva, L.Yu., Andreeva, L.A., Voronina, T.A., et al., A Family of Peptides with Analgesic Activity, RF Patent No. 2 286 169, 2005.

  • Bannon, A.W., Decker, M.W., Curzon, P., et al., [(R)-5-(2-Azetidinylmethoxy)-2-Chloropyridine]: A Novel, Orally Effective Antinociceptive Agent Acting via Neuronal Nicotinic Acetylcholine Receptors: II. In Vivo Characterization, J. Pharm. Exp. Ther., 1998, vol. 285, no. 2, pp. 787–794.

    CAS  Google Scholar 

  • Bardin, L., Bardin, M., Lavarenne, J., and Eschalier, A., Effect of Intrathectal Serotonin on Nociception in Rats: Influence of the Pain Test Used, Exp. Brain Res., 1997, vol. 113, pp. 81–87.

    Article  CAS  PubMed  Google Scholar 

  • Bowen, C.A., Fischer, B.D., Mello, N.K., and Negus, S.S., Antagonism of the Antinociceptive and Discriminative Stimulus Effects of Heroin and Morphine by 3-Methoxynaltrexone and Naltrexone in Rhesus Monkeys, J. Pharm. Exp. Ther., 2002, vol. 302, no. 1, pp. 264–273.

    Article  CAS  Google Scholar 

  • Braga, P. and Tiengo, M., Biella, G., et al., Dermorphin, A New Peptide from Amphibian Skin, Inhibits the Nociceptive Thalamic Neurons Firing Rate Evoked by Noxious Stimuli, Neurosci. Let., 1984, vol. 52, nos. 1–2, pp. 1651–1669.

    Google Scholar 

  • Broccardo, M., Erspamer, V., Falconieri Erspamer, G., et al. Pharmacological Data on Dermorphins, A New Class of Potent Opioid Peptides from Amphibian Skin, Br. J. Pharmacol., 1981, vol. 73, no. 3, pp. 625–631.

    CAS  PubMed  Google Scholar 

  • Castiglione, R., Faoro, F., Perseo, G., et al., Synthetic Peptides Related to the Dermorphins. I. Synthesis and Biological Activities of the Shorter Homologues and of Analogues of the Heptapeptides, Peptides, 1981, vol. 2, no. 3, pp. 265–269.

    Article  PubMed  Google Scholar 

  • Chernov, H.I., Wilson, D.E., Fowler, W.F., and Plummer, A.J., Non-Specificity of the Mouse Writhing Test, Arch. Int. Pharmacodyn. Ther., 1967, vol. 167, no. 1, pp. 171–178.

    CAS  PubMed  Google Scholar 

  • D’Amor, F.E. and Smith, D.L., A Method for Determining Loss of Pain Sensation, J. Pharm. Exp. Ther., 1941, vol. 72, no. 1, pp. 74–79.

    Google Scholar 

  • Darlak, K., Benovitz, D.E., Spatola, A.F., and Grzonka, Z., Dermorphin Analogs: Resistance to in Vitro Enzymatic Degradation Is Not Always Increased by Additional D-Amino Acid Substitutions, Biochem. Biophys. Res. Commun., 1988, vol. 156, no. 1, pp. 125–130.

    Article  CAS  PubMed  Google Scholar 

  • De Los Santos-Arteaga, M., Sierra-Dominguez, S.A., Fontanella, G.H. et al. Analgesia Induced by Dietary Restriction is Mediated by the κ-Opioid System, J. Neurosci., 2003, vol. 23, pp. 11 120–11 126.

    Google Scholar 

  • Gergen, K.A., Zadina, J.E., Kastin, A.J., and Paul, D., Intrathecal Tyr-W-MIF-1 Produces Potent, Naloxone-Reversible Analgesia Modulated by Alpha 2-Adrenoceptors, Eur. J. Pharmacol., 1996a, vol. 298(33), pp. 235–239.

    Article  CAS  PubMed  Google Scholar 

  • Gergen, K.A., Zadina, J.E., and Paul, D., Analgesic Effects of Tyr-W-MIF-1: A Mixed Mu2-Opioid Receptor Agonist / Mu1-Opioid Receptor Antagonist, Eur. J. Pharmacol., 1996, vol. 316, no. 1, pp. 33–38.

    Article  CAS  PubMed  Google Scholar 

  • Haffner, F., Experimental Prufung Schmerzstillender Mittel, Dtsch. Med. Wschr., 1929, vol. 55, pp. 731–733.

    Article  Google Scholar 

  • Harrison, L.M., Kastin, A.J., and Zadina, J.E., Tyr-W-MIF-1 Attenuates Down-Regulation of Opiate Receptors in SH-SY5Y Human Neuroblastoma Cells, J. Pharm. Exp. Ther., 1998, vol. 284, no. 2, pp. 611–617.

    CAS  Google Scholar 

  • Ji, Y., Murphy, A.Z., and Traub, R.J., Sex Differences in Morphine-Induced Analgesia of Visceral Pain Are Supraspinally and Peripherally Mediated, Am. J. Physiol. Regulatory. Integrative. Comp. Physiol., 2006, vol. 291, pp. R307–R314.

    CAS  Google Scholar 

  • Kastin, A.J., Stephens, E., Ehrensing, R.H., and Fischman, A.J., Tyr-MIF-1 Acts As An Opiate Antagonist in the Tail-Flick Test, Pharmacol. Biochem. Behav., 1984, vol. 21, no. (6), pp. 937–941.

    Article  CAS  PubMed  Google Scholar 

  • Kastin, A.J., Hahn, K., Erchegyi, J., et al., Differential Metabolism of Tyr-MIF-1 and MIF-1 in Rat and Human Plasma, Biochem. Pharmacol., 1994, vol. 47, no. 4, pp. 699–709.

    Article  CAS  PubMed  Google Scholar 

  • Kuraishi, Y., Horota, N., Satoh, M., and Takagi, H., Antinociceptive Effects of Intrathectal Opioids, Noradrenaline and Serotonin in Rats: Mechanical and Thermal Analgesic Tests, Brain Res., 1985, vol. 326, pp. 168–171.

    Article  CAS  PubMed  Google Scholar 

  • Makino, M., Kitano, Y., Komiyama, C., et al., Involvement of Central Opioid Systems in Human Interferon-Alpha Induced Immobility in the Mouse Forced Swimming Test, Br. J. Pharmacol., 2000, vol. 130, no. 6, pp. 1269–1274.

    Article  CAS  PubMed  Google Scholar 

  • Melchiorri, P. and Negri, L., The Dermorphin Peptide Family, Gen. Pharmacol., 1996, no. 7, pp. 1099–1107.

  • Miller, L.G. and Kastin, A.J., MIF-1 and Tyr-MIF-1 Augment GABA-Stimulated Benzodiazepine Receptor Binding, Peptides, 1987, vol. 8, no. (5), pp. 751–755.

    Article  CAS  PubMed  Google Scholar 

  • Negus, S.S., Pasternak, G.W., Koob, G.F., and Weinger, M.B., Antagonist Effects of Beta-Funaltrexamine and Naloxonazine on Alfentanil-Induced Antinociception and Muscle Rigidity in the Rat, J. Pharm. Exp. Ther., 1993, vol. 264, pp. 739–745.

    CAS  Google Scholar 

  • Olsen, U.B., Eltorp, C.T., and Ingvardsen, B.K., et el. ReN 1869, A Novel Tricyclic Antihistamine, Is Active Against Neurogenic Pain and Inflammation, Eur. J. Pharmacol., 2002, vol. 435, no. 1, pp. 43–57.

    Article  CAS  PubMed  Google Scholar 

  • Paul, D., Levison, J.A., Howard, D.H., et al., Naloxone Benzoylhydrazone (NalBzoH) Analgesia, J. Pharmacol. Exp. Ther., 1990, vol. 255, no. 2, pp. 769–774.

    CAS  PubMed  Google Scholar 

  • Rossi, A., di Salle, E., Briatico, G., et al., Antinociceptive, Prolactin Releasing and Intestinal Motility Inhibiting Activities of Dermorphin and Analogues after Subcutaneous Administration in the Rat, Peptides, 1983, vol. 4, no. 4, pp. 577–580.

    Article  CAS  PubMed  Google Scholar 

  • Schiller, P.W., Nguyen, T.M., Chung, N.N., and Lemieux, C., Dermorphin Analogues Carrying an Increased Positive Net Charge in Their “Message” Domain Display Extremely High Mu Opioid Receptor Selectivity, J. Med. Chem., 1989, no. 3, pp. 698–703.

  • Shane, R., Wilk, S., and Bodnar, R.J., Modulation of Endomorphin-2-Induced Analgesia by Dipeptidyl Peptidase IV, Brain Res., 1999, vol. 815, no. 2, pp. 278–286.

    Article  CAS  PubMed  Google Scholar 

  • Stevens, C. and Yaksh, T., Spinal Action of Dermorphin, An Extremely Potent Opioid Peptide from Frog Skin, Brain Res., 1986, vol. 385, no. 2, pp. 300–304.

    Article  CAS  PubMed  Google Scholar 

  • Walker, J.M. and Hohmann, A.G., Cannabinoid Mechanisms of Pain Suppression, Handb. Exp. Pharmacol., 2005, no. 168, pp. 509–554.

  • Zadina, J.E. and Kastin, A.J., Interactions between the Antiopiate Tyr-MIF-1 and the Mu Opiate Morphiceptin at Their Respective Binding Sites in Brain, Peptides, 1985, vol. 6, no. 5, pp. 965–970.

    Article  CAS  PubMed  Google Scholar 

  • Zadina, J.E., Kastin, A.J., Krieg, E.F., J., and Coy, D.H., Characterization of Binding Sites for N-Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) in Rat Brain, Pharmacol. Biochem. Behav., 1982, vol. 17, no. 6, pp. 1193–1198.

    Article  CAS  PubMed  Google Scholar 

  • Zadina, J.E., Kastin, A.J., Ge, L.J., and Brant, I.V., Hemorphins, Cytochrophins, and Human beta-Casomorphins Bind to Antiopiate (Tyr-MIE-1) as Well as Opiate Binding Sites in Rat Brain, Life Sci., 1990, vol. 47, no. 8, pp. PL25–PL30.

    Article  CAS  PubMed  Google Scholar 

  • Zadina, J.E., Kastin, A.J., Ge, L.J., and Hackler, L., Mu, Delta, and Kappa Opiate Receptor Binding of Tyr-MIF-1 and of Tyr-W-MIF-1, Its Active Fragments, and Two Potent Analogs, Life Sci., 1994, vol. 55, no. (24), pp. L461–L466.

    Article  Google Scholar 

  • Zadina, J.E., Paul, D., Gergen, K.A., et al. Binding of Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) and Related Peptides to mu 1 and mu 2 Opiate Receptors, Neurosci. Lett., 1996, vol. 215, no. 1, pp. 65–69.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Zakusov Research Institute of Pharmacology, Russian Academy of Medical Sciences, ul. Baltiiskaya 8, Moscow, 125315, Russia

    L. S. Guzevatykh, T. A. Voronina & S. B. Seredenin

  2. Semenov Institute of Chemical Physics, Russian Academy of Sciences, ul. Kosygina 4, Moscow, 117977, Russia

    T. G. Emel’yanova

  3. Institute of Molecular Genetics, Russian Academy of Sciences, pl. Kurchatova 46, Moscow, 123182, Russia

    L. A. Andreeva, L. Yu. Alfeeva & N. F. Myasoedov

Authors
  1. L. S. Guzevatykh
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  2. T. A. Voronina
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  3. T. G. Emel’yanova
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  4. L. A. Andreeva
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  5. L. Yu. Alfeeva
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  6. S. B. Seredenin
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  7. N. F. Myasoedov
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Correspondence to L. S. Guzevatykh.

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Original Russian Text © L.S. Guzevatykh, T.A. Voronina, T.G. Emel’yanova, L.A. Andreeva, L.Yu. Alfeeva, S.B. Seredenin, N.F. Myasoedov, 2008, published in Izvestiya Akademii Nauk, Seriya Biologicheskaya, 2008, No. 1, pp. 61–67.

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Guzevatykh, L.S., Voronina, T.A., Emel’yanova, T.G. et al. Analgesic activity of dipeptide Tyr-Pro. Biol Bull Russ Acad Sci 35, 50–55 (2008). https://doi.org/10.1134/S1062359008010081

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  • DOI: https://doi.org/10.1134/S1062359008010081

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