Elsevier

Neuropharmacology

Volume 30, Issue 11, November 1991, Pages 1233-1239
Neuropharmacology

Mu and delta opiate receptors in neuronal and astroglial primary cultures from various regions of the brain—coupling with adenylate cyclase, localisation on the same neurones and association with dopamine (D1) receptor adenylate cyclase

https://doi.org/10.1016/0028-3908(91)90170-GGet rights and content

Abstract

Primary cultures, enriched in neurones or astroglial cells, from three phylogenetically different regions of the brain of the rat, the cerebral cortex, the striatum and the brain stem, were used to investigate the presence of opiate receptors, coupled to adenylate cyclase. Morphine was used as a μ-receptor agonist and [d-Ala2, d-Leu5]-enkephalin (DADLE) was used as a δ -receptor agonist.

In the neuronal cultures, both ligands inhibited the prostaglandin (PG)E1 -stimulated intracellular accumulation of cyclic AMP dose-dependently, with the most prominent effects seen in the cultures of striatum and with DADLE being more potent than morphine. The opiate receptor antagonist, naloxone reversed the effects. Morphine and DADLE, added together, inhibited the PGE1-stimulated accumulation of cyclic AMP, less than the sum of the effects of each drug. Therefore, it might be that these opioid receptors are localized together on the same neurone. Striatal neurones contained dopamine receptors coupled to cyclic AMP, as second messenger. It was shown that the D1 (dopamine) receptor-stimulated activity of adenylate cyclase was inhibited by the μ and δ opioid receptor ligands. Thus, interactions at the level of adenylate cyclase seem to exist between D1, μ and δ opiate receptors.

In the astroglial enriched cultures, DADLE inhibited the PGE1-induced accumulation of cyclic AMP, however, with a less prominent effect in the brain stem cultures. Morphine did not influence the basal or the PGE1-stimulated intracellular accumulation of cyclic AMP in the cultures used and DADLE was less effective in inhibiting the PGE1-induced accumulation of cyclic AMP in the astroglial cultures, than in the neuronal enriched cultures, indicating less developed δ receptor-second messenger efficacy in the astroglial cultures, than in the neuronal cultures. These results thus suggest the presence of δ receptors on astroglial cells in culture, while no μ receptors with cyclic AMP as second messenger were identified.

References (48)

  • K. Maderspach et al.

    Glial and neuronal opioid receptors: apparent positive cooperativity observed in intact cultured cells

    Brain Res.

    (1988)
  • G. Milligan et al.

    Development of opiate receptors and GTP-binding regulatory proteins in neonatal rat brain

    J. biol. Chem.

    (1987)
  • S. Murphy et al.

    Functional receptors for neurotransmitters on astroglial cells

    Neuroscience

    (1987)
  • B. Pearce et al.

    Astrocyte opioid receptors: Activation modifies the noradrenaline-evoked increase in 2-[14C]deoxyglucose incorporation into glycogen

    Neurosci. Lett.

    (1985)
  • R. Quirion et al.

    Autoradiographic distribution of mu and delta opiate receptors in rat brain using highly selective ligands

    Life Sci.

    (1983)
  • A.N.M. Schoffelmeer et al.

    Fentanyl isothiocyanate reveals the existence of physically associated μ- and δ -opioid receptors mediating inhibition of adenylate cyclase in rat neostriatum

    Eur. J. Pharmac.

    (1988)
  • M.D. Smigel

    Purification of the catalyst of adenylate cyclase

    J. biol. Chem.

    (1986)
  • W. Zieglgänsberger et al.

    Multiple opiate receptors on neurons of the mammalian central nervous system. In vivo and in vitro studies

    Life Sci.

    (1982)
  • J. Bockaert et al.

    Inhibition of hormonally regulated adenylate cyclase by the βγ subunit of transducin

    EMBO J.

    (1985)
  • H. Chneiweiss et al.

    Mu and delta opiate receptors coupled negatively to adenylate cyclase on embryonic neurones from the mouse striatum in primary cultures

    J. Neurosci.

    (1988)
  • J. Codina et al.

    The a subunit of the GTP binding protein Gk opens atrial potassium channels

    Science

    (1987)
  • D.M.F. Cooper et al.

    Opiate receptor-mediated inhibition of adenylate cyclase in rat striatal plasma membranes

    J. Neurochem.

    (1982)
  • R.S. Duman et al.

    Acute and chronic opiate-regulation of adenylate cyclase in brain: Specific effects in locus coeruleus

    J. Pharmac. exp. Ther.

    (1988)
  • T.M. Egan et al.

    Both μ and δ opiate receptors exist on the same neuron

    Science

    (1981)
  • Cited by (49)

    • Astrocyte proliferation is regulated by the OGF-OGFr axis in vitro and in experimental autoimmune encephalomyelitis

      2013, Brain Research Bulletin
      Citation Excerpt :

      Steine-Martin et al. (1998) reported regional differences in the expression of opioid receptors with approximately 33% of astrocytes in the cerebral cortex expressing μ-receptor immunoreactivity, while δ and κ receptors were expressed moreso in hippocampus and cerebellum than in the cortex. Other investigators have reported heterogeneity in the mRNA levels for opioid receptors (Eriksson et al., 2001; Ruzicka et al., 1995), as well as distribution of immunoreactive endogenous opioid peptides such as enkephalins and endorphins (Hauser et al., 1990; Shinoda et al., 1989) in cultured astrocytes from rodents. Thorlin et al. (1999) reported that δ-opioid receptor immunoreactivity in cultured cortical astrocytes was upregulated during mitosis, but μ- and κ-receptor staining was not observed.

    • Genomic analysis of [d-Ala<sup>2</sup>, d-Leu<sup>5</sup>] enkephalin preconditioning in cortical neuron and glial cell injury after oxygen deprivation

      2012, Brain Research
      Citation Excerpt :

      Opioid receptors are a group of G protein-coupled receptors with opioids as ligands and have four major subtypes (delta-, kappa-, mu-, nociceptin-) in the brain (Corbett et al., 2006; Dhawan et al., 1996; Waldhoer et al., 2004). Past investigations showed that mu-, delta-, kappa-receptor subtypes are expressed in primary rat cortical neurons (Eriksson et al., 1990; Eriksson et al., 1991; Ke et al., 2009; Lee et al., 2002; Zhang et al., 2002). According to recent studies, δ-opioid agonists can produce neuroprotective effects in the central nervous system (Su, 2000; Zhang et al., 2002). [

    • Morphine modulation of thrombospondin levels in astrocytes and its implications for neurite outgrowth and synapse formation

      2010, Journal of Biological Chemistry
      Citation Excerpt :

      However, the mechanisms involved in this dynamic partnership with neurons are not well characterized. The targets of opiate drugs of abuse are opioid receptors, G protein-coupled receptors that are found in astrocytes and are capable of modulating their proliferation in vitro and in vivo (43–52). Using an astrocytoma model system, C6 glioma cells, and immortalized type 1 astrocytes, we implicated phosphatidylinositol turnover, discrete PKC isoforms, different secondary messengers, and transactivation of EGFR as well as FGF receptor in μ and κ opioid receptor (MOR and KOR) activation of ERK (53–57).

    View all citing articles on Scopus
    View full text