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-enkepha lin (Leu-Enk) elicits potentiation and suppression of humoral immune respon ses through OP1 (delta) and OP2 (kappa) receptors, respectively. Interestin gly, both effects were found to be additionally dependent on OP3 (mu) recep tor function. In the present study, we have further investigated whether op ioid receptor interactions underlie the immunomodulatory effects of endogen ous 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-sele ctive antagonists and Met-Enk. Application of the OP1 antagonist ICI 174864 , but not naltrindole, resulted in suppression of the PFC response. In cont rast, i.c.v. injection of the OP2 selective antagonist nor-binaltorphimine (nor-BNI) significantly potentiated the PFC response. Both effects, presuma bly mediated by endogenous opioid peptides, were antagonized by the OP3 rec eptor antagonist beta-funaltrexamine (beta-FNA) at a dose that was devoid o f immunomodulatory activity. The immunopotentiation of the PFC response ind uced by Met-Enk was reversed by OP1 receptor antagonists, naltrindole and I CI 174864, but not by beta-FNA or nor-BNI. On the basis of these and previous findings, it may be concluded that centr al OP3 receptors are permissive for the central immunomodulatory action of endogenous opioid peptides and Leu-Enk. In contrast, the central immunoenha ncing effect of Met-Enk appears to be mediated through OP3-independent OP1 receptors. (C) 2000 Elsevier Science B.V. All rights reserved.