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

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.