Elsevier

Brain Research

Volume 686, Issue 2, 24 July 1995, Pages 239-248
Brain Research

Occurrence of the opiate alkaloid-selective μ3 receptor in mammalian microglia, astrocytes and Kupffer cells

https://doi.org/10.1016/0006-8993(95)00452-VGet rights and content

Abstract

Evidence is presented for occurrence of opiate alkaloid-selective, opioid-peptide-insensitive receptor binding sites, labeled with [3H]morphine, in primary cultures of cat microglia and of cat astrocytes, as well as on highly purified preparations of rat Kupffer cells. These receptors have been designated μ3 on the basis of their close similarity to receptors first found to be present on human peripheral blood monocytes. Exposure of the microglia to morphine and etorphine cause marked quantifiable changes in cellular morphology, including assumption of a more rounded shape and retraction of cytoplasmic processes; in contrast, several opioid peptides were without effect on morphology. The effects of morphine on microglial morphology were blocked by the opiate antagonist naloxone. These effects of drugs on morphology were as predicted for action via the μ3 receptor. Opiate alkaloid binding sites previously detected on the rat C6 glioma cell line were also characterized here as of the μ3 receptor subtype. It is proposed that μ3 receptors have broad distribution in different macrophage cell types of bone marrow lineage, including microglia and Kupffer cells. Furthermore, these receptors are not restricted to cells of bone marrow lineage, since they are also present on astrocytes.

Reference (52)

  • PerryV.H. et al.

    Macrophages and the nervous system

    Intl. Rev. Cytol.

    (1991)
  • PetersonP.K. et al.

    Morphine amplifies HIV-1 expression in chronically infected promonocytes cocultured with human brain cells

    J. Neuroimmunol.

    (1994)
  • RaffM.C. et al.

    Cell-type specific markers for distinguishing and studying neurons and the major classes of glial cells in culture

    Brain Res.

    (1979)
  • RieskeE. et al.

    Microglia and microglia-derived brain macrophages in culture: generation from axotomized rat facial nuclei, identification and characterization in vitro

    Brain Res.

    (1989)
  • StefanoG.B. et al.

    The immuneneuro-link and the macrophage: postcardiotomy delirium, HIV-associated dementia and psychiatry

    Prog. Neurobiol.

    (1994)
  • StefanoG.B. et al.

    Endogenous morphine and related opiates, a new class of chemical messengers

    Adv. Neuroimmunol.

    (1994)
  • BargJ. et al.

    Desipramine modulation of σ and opioid peptide receptor expression in glial cells

    Peptides

    (1992)
  • BargJ. et al.

    Evidence for the implication of phosphoinositol signal transduction in μ-opioid inhibition of DNA synthesis

    J. Neurochem.

    (1992)
  • BargJ. et al.

    A monoclonal anti-idiotypic antibody to opioid receptors labels desipramine-induced opioid binding sites on rat C6 glioma cells and attenuates thymidine incorporation into DNA

    Glia

    (1994)
  • BargJ. et al.

    κ-Opioid agonist modulation of [3H]thymidine incorporation into DNA: evidence for the involvement of pertussis toxin-sensitive G-protein coupled phosphoinositide turnover

    J. Neurochem.

    (1993)
  • ChaoC.C. et al.

    Priming effect of morphine on the production of tumor necrosis factor-α by microglia: implications in respiratory burst activity and human immunodeficiency virus-1 expression

    J. Pharmacol. Exp. Ther.

    (1994)
  • CrucianiR.A. et al.

    Direct coupling of opioid receptors to both stimulatory and inhibitory guanine nucleotide-binding proteins in F-11 neuroblastoma-sensory neuron hybrid cells

  • DobrenisK. et al.

    Cerebral cortex cultures from postnatal GM2 gangliosidosis cats

    Soc. Neurosci. Abstr.

    (1989)
  • FrancesB. et al.

    Morphine-6-glucoronide is more mu-selective and potent in analgesic tests than morphine

    Prog. Clin. Biol. Res.

    (1990)
  • FricchioneG.L. et al.

    Morphine and its psychiatric implications

    Adv. Neuroimmunol.

    (1994)
  • GaleP.G. et al.

    Bone marrow origin of hepatic macrophages (Kupffer cells) in humans

    Science

    (1978)
  • Cited by (73)

    • The role of gut-immune-brain signaling in substance use disorders

      2021, International Review of Neurobiology
      Citation Excerpt :

      The opioid-induced activation of glial cells could be mediated by binding at various opioid receptors expressed by glial cells. Previous work has shown that all four members of opioid receptors (μ, δ, κ and nociceptin receptors) are expressed by glial cells (Chao, Gekker, Hu, et al., 1996; Dobrenis, Makman, & Stefano, 1995; Eriksson, Hansson, & Rönnbäck, 1992; Fu, Zhu, Wang, & Wu, 2007; Gurwell, Duncan, Maderspach, et al., 1996; Maduna, Audouard, Dembélé, et al., 2019; Meyer, Paisley, Mohamed, et al., 2017; Mika, Popiolek-Barczyk, Rojewska, et al., 2014; Nam, Han, Lee, et al., 2018; Shrivastava, Cabrera, Chastain, et al., 2017; Woo, Bae, Nam, et al., 2018). However, whether or not these receptors mediate opioid-induced glial activation remains unclear.

    • Glial neuroimmune signaling in opioid reward

      2020, Brain Research Bulletin
      Citation Excerpt :

      However, only μ opioid receptors (MOR) were thought to associate with the rewarding effect of opioid drugs. Previous studies have shown that all these opioid receptors were found to be expressed by both microglia and astrocytes (Chao et al., 1996; Dobrenis et al., 1995; Eriksson et al., 1992; Fu et al., 2007; Gurwell et al., 1996; Maduna et al., 2018; Meyer et al., 2017; Mika et al., 2014; Nam et al., 2018; Shrivastava et al., 2017; Woo et al., 2018). Surprisingly, very few studies have explored if the activation of these opioid receptors may stimulate glial cell activities or not.

    • Toll-like receptors in chronic pain

      2012, Experimental Neurology
      Citation Excerpt :

      Importantly, proinflammatory central immune signaling events have been implicated in some of these behavioral consequences following opioid engagement of non-classical opioid systems. Nonetheless, immunocompetent cells within the CNS, including but not limited to, microglia (Bokhari et al., 2009; Chao et al., 1996, 1997; Horvath et al., 2010) and astrocytes (Bunn et al., 1985; Burbassi et al., 2010; Dobrenis et al., 1995; Festa et al., 2002; Hauser et al., 1996; Maderspach et al., 1995; Ruzicka et al., 1996; Thorlin et al., 1998) express opioid receptors. However, the role of the opioid receptor in initiating central immune signaling is unclear as it has been demonstrated that some TLRs (eg TLR2 and TLR4) are also capable of recognizing opioids.

    View all citing articles on Scopus
    View full text