Modulation of humoral immune responses in the rat by centrally applied Met-Enk and opioid receptor antagonists: Functional interactions of brain OP 1 , OP 2 and OP 3 receptors

Mirjana Dimitrijevi, Stanislava Stanojevi, Vesna Kovacevi-Jovanovi, Tatjana Mileti, Vesna Vuji-Redzi, Jelena Radulovi

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

We have previously demonstrated that central application of leucine- enkephalin (Leu-Enk) elicits potentiation and suppression of humoral immune responses through OP 1 (δ) and OP 2 (κ) receptors, respectively. Interestingly, both effects were found to be additionally dependent on OP 3 (μ) receptor function. In the present study, we have further investigated whether opioid receptor interactions underlie the immunomodulatory effects of endogenous opioids as well as exogenously applied methionine-enkephalin (Met- Enk). For that purpose, the plaque-forming cell (PFC) response was determined in rats injected intracerebroventricularly (i.c.v.) with opioid receptor- selective antagonists and Met-Enk. Application of the OP 1 antagonist ICI 174864, but not naltrindole, resulted in suppression of the PFC response. In contrast, i.c.v. injection of the OP 2 selective antagonist nor- binaltorphimine (nor-BNI) significantly potentiated the PFC response. Both effects, presumably mediated by endogenous opioid peptides, were antagonized by the OP 3 receptor antagonist β-funaltrexamine (β-FNA) at a dose that was devoid of immunomodulatory activity. The immunopotentiation of the PFC response induced by Met-Enk was reversed by OP 1 receptor antagonists, naltrindole and ICI 174864, but not by β-FNA or nor-BNI. On the basis of these and previous findings, it may be concluded that central OP 3 receptors are permissive for the central immunomodulatory action of endogenous opioid peptides and Leu-Enk. In contrast, the central immunoenhancing effect of Met- Enk appears to be mediated through OP 3 -independent OP 1 receptors. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)255-262
Number of pages8
JournalImmunopharmacology
Volume49
Issue number3
DOIs
StatePublished - 2000

Keywords

  • Central nervous system
  • Leucine-enkephalin
  • Methionine-enkephalin
  • OP
  • OP
  • OP
  • Opioid receptors
  • Plaque-forming cell response

ASJC Scopus subject areas

  • Pharmacology

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