Abstract
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.
Copyright 1998 Elsevier Science B.V.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
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Animals
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Binding, Competitive / drug effects
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Disease Models, Animal
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Drug Implants
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Exons / genetics
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Gene Targeting
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Immune System / drug effects*
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Immunosuppression Therapy
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Interleukin-2 / analysis
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Interleukin-2 / metabolism
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Ligands
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Macrophage Activation / drug effects
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Macrophages, Peritoneal / cytology
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Macrophages, Peritoneal / drug effects
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Macrophages, Peritoneal / immunology
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Mice
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Mice, Knockout / genetics
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Mice, Knockout / immunology*
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Mitogens / pharmacology
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Morphine / administration & dosage
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Morphine / pharmacology*
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Naltrexone / pharmacology
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Organ Size / drug effects
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Phagocytosis / drug effects
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Receptors, Opioid, mu / genetics
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Receptors, Opioid, mu / immunology*
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Receptors, Opioid, mu / physiology*
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Spleen / drug effects
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Substance-Related Disorders
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Thymidine / metabolism
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Thymus Gland / drug effects
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Tumor Necrosis Factor-alpha / analysis
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Drug Implants
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Interleukin-2
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Ligands
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Mitogens
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Receptors, Opioid, mu
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Tumor Necrosis Factor-alpha
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Naltrexone
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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Morphine
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Thymidine