MU-opioid receptor-knockout mice: role of mu-opioid receptor in morphine mediated immune functions

Brain Res Mol Brain Res. 1998 Oct 30;61(1-2):190-4. doi: 10.1016/s0169-328x(98)00212-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
  • Animals
  • Binding, Competitive / drug effects
  • Disease Models, Animal
  • Drug Implants
  • Exons / genetics
  • Gene Targeting
  • Immune System / drug effects*
  • Immunosuppression Therapy
  • Interleukin-2 / analysis
  • Interleukin-2 / metabolism
  • Ligands
  • Macrophage Activation / drug effects
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / immunology
  • Mice
  • Mice, Knockout / genetics
  • Mice, Knockout / immunology*
  • Mitogens / pharmacology
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Naltrexone / pharmacology
  • Organ Size / drug effects
  • Phagocytosis / drug effects
  • Receptors, Opioid, mu / genetics
  • Receptors, Opioid, mu / immunology*
  • Receptors, Opioid, mu / physiology*
  • Spleen / drug effects
  • Substance-Related Disorders
  • Thymidine / metabolism
  • Thymus Gland / drug effects
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Drug Implants
  • Interleukin-2
  • Ligands
  • Mitogens
  • Receptors, Opioid, mu
  • Tumor Necrosis Factor-alpha
  • Naltrexone
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Morphine
  • Thymidine