concanavalin-a and norbinaltorphimine

It has been shown that inflammation of rat paws elicits accumulation of opioid peptide beta-endorphin-containing immune cells in the inflamed subcutaneous tissue, contributing to immunocyte-produced pain suppression. However, the possible mechanisms involved in the pharmacological application of beta-endorphin in rat paw inflammation have not been investigated. The present study was set up to explore the effects of intraplantar injection of beta-endorphin on Concanavalin A-induced paw edema in two inbred rat strains, Albino Oxford (AO) and Dark Agouti (DA). Both high dose-induced suppression and low dose-induced potentiation of edema development in AO and DA rats, respectively, were blocked with antagonists specific for delta (naltrindole) and kappa (nor-binaltorphimine) opioid receptors. beta-endorphin in vitro decreased phagocytosis and increased nitric oxide (NO) production in air pouch granulocytes obtained from AO rats. However, in cells from DA rat strain beta-endorphin modulated both phagocytosis and NO production in a concentration-dependent manner. It could be concluded that the strain-dependent opposing effects of beta-endorphin on paw inflammation are mediated through delta and kappa opioid receptors and probably involve changes in the production of reactive oxygen species by inflammatory cells. Our results point to the importance of genotype for pharmacological manipulations and the development of inflammation.

Topics: Animals; beta-Endorphin; Concanavalin A; Dose-Response Relationship, Drug; Edema; Female; Granulocytes; Hindlimb; Inflammation; Male; Naltrexone; Narcotic Antagonists; Neurotransmitter Agents; Nitric Oxide; Phagocytosis; Rats; Rats, Inbred Strains; Receptors, Opioid, delta; Receptors, Opioid, kappa; Species Specificity

It has been well known that immune function is modulated by endogenous opioid peptides: beta-endorphin and enkephalins. However, the effect of dynorphin A on the immune function has not been well documented. In this study, we investigated dynorphin A in the regulation of mitogen-induced proliferation and and interleukin-2 (IL-2) production of rat splenocytes. The results showed that dynorphin A 1-13 as well as dynorphin A 1-17 enhanced concanavalin A-stimulated [(3)H] thymidine uptake 46-112% and IL-2 production in a dose-dependent fashion. These effects were reversed by naloxone and norBNI, a selective kappa-receptor antagonist. Dynorphin A reduced cyclic AMP contents in spenocytes in naloxone and norBNI reversible fashion. The data suggest that dynorphin A enhanced mitogen-stumulated lymphocyte proliferation and IL-2 production via kappa-opioid receptor and cAMP pathway.

Topics: Analgesics, Opioid; Animals; Cells, Cultured; Concanavalin A; Dynorphins; Interleukin-2; Lymphocyte Activation; Lymphocytes; Male; Naloxone; Naltrexone; Narcotic Antagonists; Peptide Fragments; Rats; Rats, Sprague-Dawley; Spleen