Beta-endorphin differentially affects inflammation in two inbred rat strains.
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.
Stanojević
Stanislava
S
Immunology Research Center Branislav Janković, Institute of Immunology and Virology Torlak, Vojvode Stepe 458, 11152 Belgrade, Serbia and Montenegro. canac@EUnet.yu
Mitić
Katarina
K
Vujić
Vesna
V
Kovacević-Jovanović
Vesna
V
Dimitrijević
Mirjana
M
D000818:Animals; D003208:Concanavalin A / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D005260:Female; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000502:physiology*; D013045:Species Specificity; D001615:beta-Endorphin / Q000494:pharmacology*
D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D003208:Concanavalin A; D009569:Nitric Oxide; C051844:norbinaltorphimine; D009271:Naltrexone; D001615:beta-Endorphin; C055382:naltrindole