Presence of Opiate Alkaloid-Selective μ3 Receptors in Cultured Astrocytes and in Brain and Retina

  • M. H. Makman
  • K. Dobrenis
  • S. Downie
  • W. D. Lyman
  • B. Dvorkin
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 402)

Abstract

Opiate alkaloid-selective receptors, insensitive to opioid peptides and differing from classical opioid receptors in other respects, mediate inhibition by morphine of activation of human peripheral blood monocytes and are present on other macrophage cell types as well, including microglia. This receptor has been tentatively designated as a µ3 subtype. The present studies provide evidence for the presence of this receptor in cultures of astrocytes derived from human fetal brain, in cultures of feline astrocytes and in an immortalized feline astrocyte cell line. Also, neonatal and adult rat striatum and other brain regions, assayed in the presence of agents that blocked classical µ, δ and κ binding sites, were found to contain additional saturable 3H-morphine binding sites that exhibited the pharmacology of µ3 receptors. Additionally, µ3 receptor sites were present in rat retina and in the avascular guinea pig retina, retinas that lack endogenous opioid peptides and that do not contain classical opioid peptide-sensitive µ, δ or κ binding sites. For each of these preparations, with 3H-morphine as ligand, binding sites were saturable and displaced by morphine, etorphine, naloxone, diprenorphine and morphine 6-glucuronide, but not by morphine 3-glucuronide, fentanyl, benzomorphans, or by enkephalins, dynorphin, β-endorphin or other opioid peptides. These sites also could be distinguished from other (µ, δ and κ) sites on the basis of sensitivity to sulfhydryl compounds. It is proposed that.µ3 receptors occur on astrocytes as well as on microglia in brain and retina, where they function to modulate responses to injury and infection, as has been proposed previously for these receptors in the immune system.

Keywords

Glutathione Morphine Retina Alkaloid Fentanyl 

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Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • M. H. Makman
    • 1
  • K. Dobrenis
    • 2
  • S. Downie
    • 3
  • W. D. Lyman
    • 3
  • B. Dvorkin
    • 1
  1. 1.Departments of Biochemistry and Molecular PharmacologyAlbert Einstein College of MedicineNew YorkUSA
  2. 2.Department of NeuroscienceAlbert Einstein College of MedicineNew YorkUSA
  3. 3.Department of PathologyAlbert Einstein College of MedicineNew YorkUSA

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