Properties of μ₃ opiate alkaloid receptors in macrophages, astrocytes, and HL-60 human promyelocytic leukemia cells

An opiate alkaloid-selective receptor, designated μ₃, mediates inhibition by morphine of activation of human peripheral blood monocytes and granulocytes. The μ₃ receptor is present on several macrophage cell types including microglia, on cultured astrocytes, and in brain and retina. Murine macrophage cell lines and human HL-60 leukemia cells contain high concentrations of these receptors. Binding of ³H-morphine to the receptor is displaced by morphine, etorphine, naloxone, diprenorphine and morphine 6- glucuronide, but not by morphine 3-glucuronide, fentanyl, benzomorphans, enkephalins, dynorphin, β-endorphin, endomorphin-1, other opioid peptides or nociceptin (orphanin FQ). The μ₃ receptor appears to be much more sensitive to inactivation by reduced glutathione than are classical μ, δ and κ receptors. Evidence is also presented for G protein-coupling of these reports. These and other data raise the possibility than the μ₃ receptor is a member of a chemokine or of another related receptor family, rather than the opioid receptor family. The affinity for morphine of μ₃ receptors of granulocytes and granulocytic-differentiated HL-60 cells is markedly enhanced in the presence of levorphanol and certain benzomorphans. In contrast, receptors of monocytes, macrophage cell lines, microglia, macrophage- differentiated HL-60 cells and astrocytes are not affected by levorphanol or benzomorphans. It is concluded that μ₃ receptors of granulocytic and promelocytic cells differ from those of macrophage and astrocyte cell types, possibly due to differences in receptor subtype or to the presence of an additional component in the granulocytic and promyelocytic cells.