Variation in the analgesic activity of opioid peptide fragments in correlation with the amino acidic sequence

• Authors: Irina Jaba , Bogdan Tamba , Georgios Manolidis , Ostin Mungiu
• Languages of publication: EN

Abstracts

EN

Short fragments of typical or atypical opioid peptides, lacking the whole four amino acid sequence of the enkephalin motif, can preserve a significant percentage of the analgesic activity of the original peptides. This paper investigates the importance of the amino-acidic sequence of minimum structure typical opioid peptides for the analgesic activity. Different groups of rats were treated with 1) Gly-Tyr, 0.5 mg/rat i.t., 2) Tyr-Gly, 0.5 mg/rat i.t., 3) Tyr-Gly-Gly, 0.5 mg/rat i.t., 4) Gly-Gly-Phe-Leu, 0.5 mg/rat i.t., 5) Leu-enkephalin, 0.5 mg/rat i.t.. The analgesic effect of the tested substances was appreciated through the nociceptive threshold for thermal (plantar test) and mechanical nociception (algesimetric test). Fragments of typical opioid peptides elicited antinociceptive activity only when a tyrosine residue was present at the N-terminal end of the amino-acidic sequence. The presence of Nterminal tyrosine provides affinity for the opioid receptors and significant analgesic activity. The intensity of the antinociceptive effect was directly proportional with the length of the amino-acidic sequence. The inhibition of the analgesic effect by previous administration of naloxone proves that this effect is mediated through the opioid system.

Keywords

EN

Analgesia; amino acid sequence; nociception; opioid peptides; tyrosine

• Publisher: De Gruyter Open
• Journal: Open Medicine
• Year: 2007
• Volume: 2
• Issue: 4
• Pages: 417-429

Dates

published

1 - 12 - 2007

online

1 - 12 - 2007

Contributors

author

Irina Jaba

• Center for the Study and Therapy of Pain, Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, 700115, Iasi, Romania

author

Bogdan Tamba

• Center for the Study and Therapy of Pain, Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, 700115, Iasi, Romania

author

Georgios Manolidis

• Center for the Study and Therapy of Pain, Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, 700115, Iasi, Romania

author

Ostin Mungiu

• Center for the Study and Therapy of Pain, Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, 700115, Iasi, Romania

References

• [1] O.C. Mungiu: “Repere fiziologice/Physiological landmarks”, In: O.C. Mungiu (Ed.), Tratat de algeziologie/ Algesiology Textbook, Polirom Publishing, Iasi, (2002), pp. 64–161.
• [2] I.M. Jaba, D. Vasincu, G. Manolidis, I. Haulica and O.C. Mungiu: “Experimental data regarding the implications of certain minimum structure enkephalin-like peptides in nociceptive processing”, Rom. J. Physiol., Vol. 41, (2004), pp. 119–126.
• [3] P.H. Janak and J.L. Martinez: “Only tyrosine-containing metabolites of [Leu]enkephalin impair active avoidance conditioning in mice”, Pharmacol. Biochem. Behav., Vol. 37, (1990), pp. 655–659. http://dx.doi.org/10.1016/0091-3057(90)90542-P[Crossref]
• [4] V.Y.H. Hook: “Protease Pathways in Peptide Neurotransmission and Neurodegenerative Diseases”, Cell. Mol. Neurobiol., Vol. 26, (2006), pp. 447–467. http://dx.doi.org/10.1007/s10571-006-9047-7[Crossref]
• [5] A.A. Houdi and G.R. Van Loon: “Haloperidol-induced increase in striatal concentration of the tripeptide, Tyr-Gly-Gly, provides an index of increased enkephalin release in vivo”, J. Neurochem., Vol. 54, (1990), pp. 1360–1366. http://dx.doi.org/10.1111/j.1471-4159.1990.tb01970.x[Crossref]
• [6] G. Schulteis and J.L. Martinez: “[Leu]enkephalin and its metabolite, Tyr-Gly-Gly, impair active avoidance retention”, Pharmacol. Biochem. Behav., Vol. 42, (1992), pp. 523–527. http://dx.doi.org/10.1016/0091-3057(92)90149-A[Crossref]
• [7] H. Teschemacher: “Atypical opioid peptides”, In: A. Hertz (Ed.): Opioids I. Handbook of Experimental Pharmacology, Springer-Verlaag, Berlin, 1993, pp. 499–528.
• [8] P. Pattee, A.E. Ilie, S. Benyhe, T. Geza, A. Borsodi and S.R. Nagalla: “Cloning and characterization of Xen-dorphin prohormone from Xenopus laevis. A new opioid-like prohormone distinct from proenkephalin and prodynorphin”, J. Biol. Chem., Vol. 52, (2003), pp. 53098–53104. http://dx.doi.org/10.1074/jbc.M306724200[Crossref]
• [9] P. Melchiorri and L. Negri: “The dermorphin peptide family”, Gen. Pharmacol., Vol. 27, (1996), pp. 1099–1107. [Crossref]
• [10] G. Horvath, M. Szikszay, C. Tomboly and G. Benedek: “Antinociceptive effects of intrathecal endomorphin-1 and-2 in rats”, Life Sci., Vol. 65, (1999), pp. 2635–2641. http://dx.doi.org/10.1016/S0024-3205(99)00532-9
• [11] H. Mizoguchi, L.F. Tseng, T. Suzuki, I. Sora and M. Narita: “Differential Mechanism of G-protein activation induced by endogenous miu-opioid peptides, endomorphin and beta-endorphin”, Jpn. J. Pharmacol., Vol. 89, (2002), pp. 229–234. http://dx.doi.org/10.1254/jjp.89.229[Crossref]
• [12] B. Biondi, E. Giannini, L. Negri, P. Melchiorri, R. Lattanzi, F. Rosso, L. Ciocca and R. Rocchi: “Opioid Peptides: Synthesis and Biological Activity of New Endomorphin Analogues”, Int. J. Pept. Res. Ther., Vol. 12, (2006), pp. 145–151. http://dx.doi.org/10.1007/s10989-006-9015-6[Crossref]
• [13] R.J. Vavrek, L.H. Hsi, E.J. York, M.E. Hall and J.M. Stewart: “Minimum structure opioids-dipeptide and tripeptide analogs of the enkephalins”, Peptides, Vol. 2, (1981), pp. 303–308. http://dx.doi.org/10.1016/S0196-9781(81)80124-6[Crossref]
• [14] M.G. Clemente, S. De Virgiliis., J.S. Kang, R. Macatagney, M.P. Musu, M.R. Di Pierro, S. Drago, M. Congia and A. Fasano: “Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function”, Gut, Vol. 52, (2003), pp. 218–223. http://dx.doi.org/10.1136/gut.52.2.218[Crossref]
• [15] M. Yoshikawa, M. Takahashi and S. Yang: “Delta opioid peptides derived from plant proteins”, Curr. Pharm. Design, Vol 9, (2003), pp. 1325–1330. http://dx.doi.org/10.2174/1381612033454838[Crossref]
• [16] I.E. Goldberg, G.C. Rossi, S.R. Letchworth, J.P. Mathis, J. Ryan-Moro, L. Leventhal, W. Su, D. Emmel, E.A. Bolan and G.W. Pasternak: “Pharmacological Characterisation of Endomorphin-1 and Endomorphin 2 in Mouse Brain”, J. Pharmacol. Exp. Ther., Vol 286, (1998), pp. 1007–1013.
• [17] S. Sakurada, T. Hayashi and M. Yuhki: “Differential Antinociceptive Effects Induced by Intrathecally-Administered Endomorphin-1 and Endomorphin 2 in Mice”, Jpn. J. Pharmacol., Vol. 89, (2002), pp. 221–223. http://dx.doi.org/10.1254/jjp.89.221
• [18] T. Nishiyama and K. Hanaoka: “Reproducibility of the Drug Effects over Time on Chronic Lumbar Epidural Catheterization in Rats”, Anesth. Analg., Vol. 89, (1999), pp. 1492–1494. http://dx.doi.org/10.1097/00000539-199912000-00033[Crossref]
• [19] T. Yaksh and T.A. Rudy: “Chronic catheterization of the spinal subarachnoid space”, Physiol. Behav., Vol. 17, (1976), pp. 1031–1036. http://dx.doi.org/10.1016/0031-9384(76)90029-9[Crossref]
• [20] K. Hanif, K. Gupta, S. Gupta, Y.K. Gupta, S. Maiti and S. Pasha: “Chimeric peptide of met-enkephalin and FMRFa: effect of chlorination on conformation and analgesia”, Neurosci Lett., Vol. 403, (2006), pp. 131–135. http://dx.doi.org/10.1016/j.neulet.2006.04.029[Crossref]
• [21] A. Janecka, J. Fichna, M. Mirowski and T. Janecki: “Structure-activity relationship, conformation and pharmacology studies of morphiceptin analogues-selective mu-opioid receptor ligands”, Mini. Rev. Med. Chem., Vol. 2, (2002), pp. 565–572. http://dx.doi.org/10.2174/1389557023405567[Crossref]
• [22] A.W. Lipkowski, A. Misicka, D. Kosson, P. Kosson, M. Lachwa-From, A. Brodzik-Bienkowska and V.J. Hruby: “Biological properties of a new fluorescent biphalin fragment analogue”, Life Sci. Vol., 70, (2002) pp. 893–897. http://dx.doi.org/10.1016/S0024-3205(01)01467-9[Crossref]
• [23] A. Misicka, A. Lipkowski, R. Horvath, P. Davis, F. Porreca, H.I. Yamamura and V.J. Hruby: “Structure-activity relationship of biphalin. The synthesis and biological activities of new analogues with modifications in positions 3 and 4”, Life Sci., Vol. 60, (1997), pp. 1263–1269. http://dx.doi.org/10.1016/S0024-3205(97)00069-6[Crossref]
• [24] B. Baldelli, L. Vecchio, M.G. Bottone, G. Muzzonigro, M. Biggiogera and M. Malatesta: “The effect of the enkephalin DADLE on transcription does not depend on opioid receptors”, Histochem. Cell. Biol., Vol. 126, (2006), pp. 189–197. http://dx.doi.org/10.1007/s00418-006-0145-x[Crossref]
• [25] C. Sakurada: “Development of a New Analgesic Based on Metabolism of Endomorphin, an Endogenous Opioid Peptide”, Yakuga Zasshi, Vol. 124, (2004), pp. 549–554. http://dx.doi.org/10.1248/yakushi.124.549[Crossref]

Identifiers

DOI

10.2478/s11536-007-0036-0