Summary
An opiate alkaloid-selective receptor, designated µ3, mediates inhibition by morphine of activation of human peripheral blood monocytes and granulocytes. The µ3receptor 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, ´ and K receptors. Evidence is also presented for G protein-coupling of these receptors. These and other data raise the possibility that the µ3receptor is a member of a chemokine or of another related receptor family, rather than the opioid receptor family.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Lopker, A., Abood, L. G., Hoss, W. and Lionetti, F. J. (1980). Stereoselective muscarinic acetylcholine and opiate receptors in human phagocytic leukocytes. Biochem. Pharmacol. 29:1361–1365.
Madden, J. J., Donahoe, R. M., Zwemer-Collins, J., Shafer, D. A. and Falek, A. (1987). Binding of naloxone to human T lymphocytes. Biochem. Pharmacol. 36:4103–4109.
Roy, S., Bang-Lun G., Loh, H. H. and Lee, N. M. (1992). Characterization of [3H]morphine binding to interleukin-1-activated thymocytes. J. Pharmacol. Exp. Therap. 263:45–456.
Makman, M. H. (1994) Morphine Receptors in Immunocytes and Neurons, Adv. Neuroimmunol., 4:69–82.
Stefano, G. B., Scharrer, B., Smith, E. M., Hughes, T. K., Jr., Magazine, H. I., Bilfmger, T. V., Hartman, A. R., Friccione, G. L., Liu, Y., and Makman, M. H. (1996) Opioid and opiate immunoregulatory processes. Crit. Revs. in Immunol. 16: 109–144.
Stefano, G. B., Digenis, A., Spector, S., Leung, M. K., Bilflnger, T. V., Makman, M. H., Scharrer, B. and Abumrad, N. N. (1993). Opiate-like substances in an invertebrate, an opiate receptor on invertebrate and human immunocytes, and a role in immunosuppression. Proc. Natl. Acad. Sci. U.S.A. 90:11099–11103.
Cruciani, R.A., Dvorkin, B., Klinger, H.P. and Makman, M.H. (1994) Presence in neuroblastoma cells of a µ3receptor with selectivity for opiate alkaloids but without affinity for opioid peptides. Brain Res. 667:229–237.
Makman, M. H., Bilfmger, T. V. and Stefano, G. B. (1995) Human granulocytes contain an opiate alkaloid-selective receptor mediating inhibition of cytokine-induced activation and chemotaxis. J. Immunol. 154:1323–1330.
Makman, M. H., Dvorkin, B. and Stefano, G.B. (1995) Murine macrophage cell lines contain µ3opiate receptors. Eur. J. Pharmacol. 273:R5–R6.
Dobrenis, K., Makman, M.H. and Stefano, G.B. (1995) Occurrence of the opiate alkaloid-selective µ3 receptor in mammalian microglia and astrocytes in culture and in Kupffer cells. Brain Res. 686: 239–248.
Makman, M. H., Dobrenis, K., Downie, S., Lyman, W. D., and Dvorkin, B. (1996) Presence of opiate alkaloid-selective µ3in cultured astrocytes and in brain and retina. Adv. Exp. Biol. & Med. 402:23–28.
Breitman, T. R., Selonik, S. E., and Collins, S. J. (1980) Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc. Natl. Acad. Sci. USA 77: 2936–2940.
Katagari, K., Yokoyama, K. K., Yamamoto, T., Omura, S., Irie, S., Kayagiri, T. (1996) Lyn and Fgr protein-tyrosine kinases prevent apoptosis during retinoic acid-induced granulocytic differentiation. J. Biol. Chem. 271:11557–11562.
Rovera, G., Santoli, D., and Damsky, C. (1979) Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with phorbol diester. Proc. Natl. Acad. Sci. USA 76: 2779–2783.
Gierschik, P., Moghtader, R., Straub, C., Dieterich, K., and Jakobs, K. H. (1991) Signal amplification in HL-60 granulocytes—Evidence that the chemotactic peptide receptor catalytically activates guanine-nu-cleotide-binding regulatory proteins in native plasma membranes. Eur. J. Biochem. 197: 735–732.
Cruciani, R. A., Dvorkin, B., Morris, S. A., Crain, S. M. and Makman, M. H. (1993). Direct coupling of opioid receptors to both stimulatory and inhibitory guanine nucleotide-binding proteins in F-11 neuroblas-toma-sensory neuron hybrid cells. Proc. Natl. Acad. Sci. U.S.A. 90:3019–3023.
Simmons, M. L., and Murphy, S. (1992) Induction of nitric oxide synthase in glial cells. J. Neurochem. 59: 897–905.
Lee, S. G., Liu, W., Dickson, D. W., Brosnan, C. F., and Berman, J. W. (1993) Cytokine production by human fetal microglia and astrocytes; differential induction by lipopolysaccharide and IL-1 β. J. Immunol. 150:2659–2667.
Patrizzio, M., Costa, T., and Levi, G. (1995) Interferon-γ and lipopolysaccharide reduce cAMP responses in cultured glial cells: reversal by a type IV phosphodiesterase inhibitor. Glia 14: 94–100.
Collins, S. J. (1987) The HL-60 promyelocytic leukemia cell line: proliferation, differentiation, and cellular oncogene expression. Blood 70: 1233–1244.
Mulder, G. J. (1992) Pharmacological effects of drug conjugates: is morphine 6-glucuronide an exception? Trends Pharmacol. Sci. 13: 302–304..
Zadina, J. E., Hackler, L., Ge, L.-J., and Kastin, A. J. (1997) A potent and selective endogenous agonist for the ε-opiate receptor. Nature 386: 499–502.
Makman, M. H., Lyman, W. D., and Dvorkin, B. (1997) Presence and characterization of nociceptin (or-phanin FQ) receptor binding in adult rat and human fetal hypothalamus. Brain Res. 762: 247–250.
Makman, M. H., and Dvorkin, B. (1997) Presence of nociceptin (orphanin FQ) receptors in rat retina: comparison with receptors in striatum. Eur. J. Pharmacol. In Press.
Chao, C. C., Gekker, G., Sheng, W. S., Hu, S., Tsang, M., and Peterson, P. K. (1994) 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. Therap. 269: 198–203.
Pasternak, G. W. 1986. Multiple mu opiate receptors: biochemical and pharmacological evidence for multiplicity. Biochem. Pharmacol. 35:361.
Stefano, G. B., Hartman, A., Bilfinger, T. V., Magazine, H. I., Liu, Y., Casares, F., and Goligorsky, M. S. (1995) Presence of the m3 opiate receptor in endothelial cells: coupling to nitric oxide production and vasodilation. J. Biol. Chem. 270: 30290–30293.
Magazine, H. I., Liu, Y., Bilfinger, T. V., Fricchione, G. L., and Stefano, G.B. (1996) Morphine-induced conformational changes in human monocytes, granulocytes and endothelial cells and in invertebrate immunocytes and microglia are mediated by nitric oxide. J. Immunnol. 156: 4845–4850.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer Science+Business Media New York
About this chapter
Cite this chapter
Makman, M.H., Dobrenis, K., Surratt, C.K. (1998). Properties of µ3 Opiate Alkaloid Receptors in Macrophages, Astrocytes, and HL-60 Human Promyelocytic Leukemia Cells. In: Friedman, H., Madden, J.J., Klein, T.W. (eds) Drugs of Abuse, Immunomodulation, and Aids. Advances in Experimental Medicine and Biology, vol 437. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5347-2_15
Download citation
DOI: https://doi.org/10.1007/978-1-4615-5347-2_15
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7439-8
Online ISBN: 978-1-4615-5347-2
eBook Packages: Springer Book Archive