Modulation of humoral immune responses in the rat by centrally applied Met-Enk and opioid receptor antagonists: Functional interactions of brain OP₁, OP₂ and OP₃ receptors

We have previously demonstrated that central application of leucine- enkephalin (Leu-Enk) elicits potentiation and suppression of humoral immune responses through OP₁ (δ) and OP₂ (κ) receptors, respectively. Interestingly, both effects were found to be additionally dependent on OP₃ (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 OP₁ antagonist ICI 174864, but not naltrindole, resulted in suppression of the PFC response. In contrast, i.c.v. injection of the OP₂ selective antagonist nor- binaltorphimine (nor-BNI) significantly potentiated the PFC response. Both effects, presumably mediated by endogenous opioid peptides, were antagonized by the OP₃ 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 OP₁ 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 OP₃ 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 OP₃-independent OP₁ receptors. (C) 2000 Elsevier Science B.V.