MU-opioid receptor-knockout mice: role of mu-opioid receptor in morphine mediated immune functions.
The role of the mu-opioid receptor in immune function was investigated using mu-opioid receptor knockout mice (MOR-KO). Morphine modulation of several immune functions, including macrophage phagocytosis and macrophage secretion of TNF-alpha, was not observed in the MOR-KO animals, suggesting that these functions are mediated by the classical mu-opioid receptor. In contrast, morphine reduction of splenic and thymic cell number and mitogen-induced proliferation were unaffected in MOR-KO mice, as was morphine inhibition of IL-1 and IL-6 secretion by macrophages. These latter results are consistent with morphine action on a naloxone insensitive morphine receptor, a conclusion supported by previous studies characterizing a nonopioid morphine binding site on immune cells. Alternatively, morphine may act either directly or indirectly on these cells, by a mechanism mediated by either delta or kappa opioid receptors.
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Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. royxx002@gold.tc.umn.edu
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D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004195:Disease Models, Animal; D004343:Drug Implants; D005091:Exons / Q000235:genetics; D018390:Gene Targeting; D007107:Immune System / Q000187:drug effects*; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000032:analysis / Q000378:metabolism; D008024:Ligands; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics / Q000276:immunology*; D008934:Mitogens / Q000494:pharmacology; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D013154:Spleen / Q000187:drug effects; D019966:Substance-Related Disorders; D013936:Thymidine / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D004343:Drug Implants; D007376:Interleukin-2; D008024:Ligands; D008934:Mitogens; D017450:Receptors, Opioid, mu; D014409:Tumor Necrosis Factor-alpha; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D013936:Thymidine