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Article / Publication Details
Methionine-enkephalin (Met-Enk) induces notable alterations in immune and central nervous system functions. The present study was conducted in order to compare peripheral and central effects of Met-Enk on nonspecific immunity, open field behavior and pain perception in the rat. The results showed that 0.2 mg/kg of Met-Enk given intraperitoneally (i.p.) increased concanavalin A (Con-A)-induced paw edema and enhanced basal and phorbol myristate acetate (PMA)-stimulated H2O2 production of peritoneal macrophages. Met-Enk-induced immunopotentiation was antagonized by anti-Met-Enk antibodies (anti-Met-Enk-Ig) and quaternary naltrexone (qNtx). Met-Enk injected i.p. produced an increase of horizontal and vertical locomotor activity in the open field that was reversed by i.p. administration of anti-Met-Enk-Ig and qNtx. The dose of 0.2 mg/kg of Met-Enk applied i.p. did not affect the number of writhes in the test of analgesia. Intracerebroventricular (i.c.v.) injection of Met-Enk, given in a dose that was previously shown to be immunostimulatory, enhanced only basal H2O2 production of peritoneal macrophages, and anti-Met-Enk-Ig antagonized this effect. Besides, i.c.v. treatment with anti-Met-Enk-Ig increased and decreased H2O2 production of peritoneal macrophages under basal and stimulated conditions, respectively. Met-Enk and anti-Met-Enk-Ig injected i.c.v. did not influence activity in the open field and pain sensitivity. Thus, the i.c.v. dose of Met-Enk that was sufficient to modulate immune functions did not influence behavior. It may be concluded that Met-Enk modulated nonspecific immune responses and open field behavior by peripheral mechanisms.
Article / Publication Details
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- Janković BD, Marić D: Enkephalins and autoimmunity: Differential effects of methionine-enkephalin on experimental allergic encephalomyelitis in Wistar and Lewis rats. J Neurosci Res 1988;18:88–94.
- Janković BD, Radulović J: Enkephalins, brain and immunity: Modulation of immune responses by methionine-enkephalin injected into the cerebral cavity. Int J Neurosci 1992;67:241–270.
- Radulović J, Mančev Z, Stanojević S, Vasiljević T, Kovačević-Jovanović V, Pešić G: Modulation of humoral immune response by central administration of leucine-enkephalin: Effects of μ, δ and κ opioid receptor antagonists. J Neuroimmunol 1996;65:155–161.
- Adamson WT, Windh RT, Blackford S, Kuhn CM: Ontogeny of mu- and kappa-opiate receptor control of the hypothalamo-pituitary-adrenal axis. Endocrinology 1991;129: 959–964.
- Carr DJ, Gebhardt BM, Paul D: Alpha adrenergic and mu-2 opioid receptors are involved in morphine-induced suppression of splenocyte natural killer activity. J Pharmacol Exp Ther 1993;264:1179–1186.
- Fecho F, Dykstra LA, Lysle DT: Evidence for beta adrenergic receptor involvement in the immunomodulatory effects of morphine. J Pharmacol Exp Ther 1993;265:1079–1087.
- Lopker A, Abood LG, Hoss W, Lionetti FJ: Stereoselective muscarinic, acetylcholine and opiate receptors in human phagocytic leukocytes. Biochem Pharmacol 1980;29:1361–1365.
- Ansiello CM, Roda, LG: Leu-enkephalin binding to cultured human T-lymphocytes. Cell Biol Int Rep 1984;8:353–362.
- Mathews PM, Froelich JC, Sibbit LW, Bankhurst DA: Enhancement of nature cytotoxicity by β-endorphin. J Immunol 1983;130:1658–1662.
- Carr DJ, DeCosta BR, Kim C-H, Jacobson AE: Opioid receptors on cells of the immune system: Evidence for δ- and κ-classes. J Endocrinol 1989;122:161–168.
- Radulescu RT, DeCosta BR, Jacobson AE, Rice KC, Blalock JE, Carr DJ: Biochemical and functional characterization of a μ-opioid receptor binding site on cells of the immune system. PNEI 1991;4:166–179.
- Gavériaux C, Peluso J, Simonin F, Laforet J, Kieffer B: Identification of κ- and δ-opioid transcripts in immune cells. FEBS Lett 1995;369:272–276.
- Hsueh C-M, Hiramoto RN, Ghanta VK: The central effect of methionine-enkephalin on NK cell activity. Brain Res 1992;578:142–148.
- Janković BD, Marić D: Enkephalins as regulators of inflammatory immune reactions; in Sharrer M, Smith ME, Stefano GB (eds): Neuropeptides and Immunoregulation. Berlin, Springer, 1994, pp 76–100.
- Janković BD, Marić D: Enkephalins modulate in vivo immune reactions through delta- and mu-opioid receptors. Ann NY Acad Sci 1988;540:691–693.
- Hucklebridge FH, Hudspith BN, Muhamed J, Lydyard PM, Brostoff J: Methionine-enkephalin stimulates in vitro proliferation of human peripheral lymphocytes via δ-opioid receptors. Brain Behav Immun 1989;3:183–189.
- Casellas AM, Guardiola H, Renaud FL: Inhibition by opioids of phagocytosis in peritoneal macrophages. Neuropeptides 1991;18:35–40.
- Fischer EG, Falke NE: Endogenous opioid peptides stimulate human phagocytes: Functional and binding studies. Adv Biosci 1987;66:373–379.
- Foris G, Medgyesi GA, Gyimesi E, Hauck M: Met-enkephalin induced alterations of macrophage functions. Mol Immunol 1984;21:747–750.
- Radulović J, Dimitrijević M, Laban O, Stanojević S, Vasiljević T, Kovačević-Jovanović V, Marković BM: Effect of met-enkephalin and opioid antagonists on rat macrophages. Peptides 1995;16:1209–1213.
- Corbett AD, Gillan MGC, Kosterlitz HW, McKnight AT, Paterson SJ, Robson LE: Selectivities of opioid peptide analogues as agonists and antagonists at the δ-receptor. Br J Pharmacol 1984;83:271–279.
- Radulović J, Miljević Č, Djergović D, Vujić V, Antić J, von Hörsten S, Janković BD: Opioid receptor-mediated suppression of humoral immune response in vivo and in vitro: involvement of κ opioid receptors. J Neuroimmunol 1995;57:55–57.
- Churchill L, Roques BP, Kalivas PW: Dopamine depletion augments endogenous opioid-induced locomotion in the nucleus accumbens using both μ and δ opioid receptors. Psychopharmacology 1995;120:347–355.
- Leventhal L, Cole JL, Bodnar RJ: Reductions in locomotor activity following central opioid receptor subtype antagonists in rats. Physiol Behav 1996;60:833–836.
- Beluzzi JD, Gran N, Garasky V, Sarantakis D, Wise CD, Sein L: Analgesia induced in vivo by central administration of enkephalin in rat. Nature 1976;260:625–626.
- Dauge V, Samir A, Cupo A, Roques BP: Peripheral stimulation of CCK-B receptors by BC264 induces a hyperexploration, dependent on the partial derivative opioid system in the nucleus accumbens of rat. Neuropharmacology 1999;38:999–1007.
- Radulović J, Vujić V, Stanojević S, Vasiljević T, Kovačević-Jovanović V, Radulović M: Naturally occurring anti-peptide antibodies in the rat: Anti-Met-Enk antibodies; in Lukić ML, Čolić M, Mostarica-Stojković M, Čuperlović K (eds): Immunoregulation in Health and Disease. London, Academic Press, 1997, pp 197–203.
- Pick E, Mizel D: Rapid microassays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. J Immunol 1981;46:211–226.
- Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–275.
- Whittle BA: The use of changes in capillary permeability in mice to distinguish between narcotic analgesics. Br J Pharmacol 1964;22:246–253.
- Janković BD, Marić D: Enkephalins and immunity. I. In vivo suppression and potentiation of humoral immune response. Ann NY Acad Sci 1987;496:115–125.
- Stein C, Hassan AHS, Przewlocki R, Gramsch C, Peter K, Herz A: Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation. Proc Natl Acad Sci USA 1990;87:5935–5939.
- Schiable HG, Grubb BD: Afferent and spinal mechanisms of joint pain. Pain 1993;55:5–54.
- Blalock JE, Smith EM: Human leukocyte interferon: Structural and biological relatedness to adrenocorticotropin hormone and endorphins. Proc Natl Acad Sci USA 1980;77:5972–5974.
- Schäfer M, Carter L, Stein C: Interleukin 1 beta and corticotropin-releasing factor inhibit pain by releasing opioids from immune cells in inflamed tissue. Proc Natl Acad Sci USA 1994;91:4219–4223.
- Van Epps DE, Saland L: β-Endorphin and met-enkephalin stimulate human peripheral blood mononuclear cell chemotaxis. J Immunol 1984;132:3046–3053.
- Kowalski J: Augmenting effect of opioids on nitrite production by stimulated murine macrophages. Neuropeptides 1998;32:287–291.
- Miller B: Delta opioid receptor expression is induced by concanavalin A in CD4+ T cells. J Immunol 1996;157:5324–5328.
- House RV, Thomas PT, Bhargava HN: A comparative study of immunomodulation produced by in vitro exposure to delta opioid receptor agonist peptides. Peptides 1996;17:75–81.
- Vujić V, Pešić G, Radulović J, Janković BD: Central modulation of humoral and cell mediated immune responses in the rat by endogenous enkephalin. Iugoslav Physiol Pharmacol Acta 1995;31:285–293.
- Hagi K, Uno K, Inaba K, Muramatsu S: Augmenting effects of opioid peptides on murine macrophage activation. J Neuroimmunol 1994;50:71–76.
- Roscetti G, Possenti R, Bassano E, Roda LG: Mechanisms of leu-enkephalin hydrolysis in human blood. Life Sci 1984;45:193–197.
- Pardrige WM, Mietus LJ: Enkephalin and blood brain barrier: studies of binding and degradation in isolated microvessels. Endocrinology 1981;109:1138–1145.
- Planas ME, Rodriguez L, Sanchez S, Pol O, Puig MM: Pharmacological evidence for the involvement of the endogenous opioid system in the response to local inflammation in the rat paw. Pain 1995;60:67–71.
- Michael-Titus A, Dourmap N, Costentin J, Schwartz JC: Role of delta-opioid receptors in the effects of inhibitors of enkephalin-degrading peptidases on the horizontal and vertical components of locomotion in mice. Neuropeptides 1990;15:89–100.
- Browne RG, Segal DS: Behavioral effects of opiates and opioid peptides. Biol Psychiatr 1980;15:77–86.
- Schulteis G, Martinez JL: Peripheral modulation of learning and memory: enkephalins as a model system. Psychopharmacology 1992;109:347–364.
- Klitenick MA, Wirtschafter D: Behavioral and neurochemical effects of opioids in the paramedian midbrain tegmentum including the median raphe nucleus and ventral tegmental area. J Pharmacol Exp Ther 1995;273:327–336.
- Pešić S, Pešić G, Mančev Z, Malobabić Z: Effect of met-enkephalin on rat visceral pain. Acta Med Mediane 1996;2:5–11.