T-cell E-receptor Modulation by Opiates, Opioids and Other Behaviorally Active Substances

  • Robert Donahoe
  • John Madden
  • Felicia Hollingsworth
  • David Shafer
  • Arthur Falek


Homeostasis has been defined as a state of metastable equilibrium wherein the constancy of the internal milieu is forever being challenged 1,2 Using this definition, any antihomestatic stimulus may be regarded as a stressor2. As reviewed eleswhere 3,4, the neural and immune systems share many basic physiologic processes in response to environmental stressors. The ultimate purpose of the neuroimmune system is maintenance of homeostasis. Neurons and lymphocytes are pluripotent sensory cells5 capable of eliciting and responding to various hormone and hormonelike peptides that have systemic and local effects characteristic of endocrine, exocrine, and paracrine functions. The primary physiologic basis for the adaptability of the neuroimmue system resides in a complex network of receptor-response systems. This review focuses on the means by which opiates and other behaviorally active substances, as examples of environmental stressors of known behavioral modifying capacity, can modulate receptor activity on T-cell lymphocytes. This capacity for receptor modulation appears to be a primary means by which opiates and like factors evoke both neurobiological and immunobiological changes in host physiology and responsive behavior.


Opiate Receptor Sheep Erythrocyte Heroin Addict Kinetic Assay Phase Transition Phenomenon 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    W. B. Cannon, Organization for physiological homeostasis, Physiol. Rev. 9: 399 (1929).Google Scholar
  2. 2.
    T. L. Sourkes, Neurotransmitters and central regulation of adrenal functions, Biol. Psychiatry 20: 182 (1985).Google Scholar
  3. 3.
    R. Ader, “Psyehoneuroimmunology,” Academic Press, N.Y. (1981).Google Scholar
  4. 4.
    R. Guillemin, M. Cohn, and T. Melnechuk, “Neural modulation of immunity,” Raven Press, N. Y. (1984).Google Scholar
  5. 5.
    J. E. Blalock, The immune system as a sensory organ, J. Immunol. 132: 1067 (1985).Google Scholar
  6. 6.
    J. Wybran, T. Appelboom, J.-P. Famaey, and A. Govaerts, Suggestive evidence for receptors for morphine and methionine-enkephalin on normal human T-lymphocytes, J. Immunol. 123: 1068 (1980).Google Scholar
  7. 7.
    R. J. McDonough, J. J. Madden, A. Falek, D. A. Shafer, M. Pline, D. Gordon, P. Bokos, J. C. Kuehnle, and J. Mendelson, Alteration of T and null lymphocyte frequencies in the peripheral blood of human opiate addicts: In vivo evidence for opiate receptor sites on T lymphocytes, J. Immunol. 125: 2539 (1980).PubMedGoogle Scholar
  8. 8.
    G. C. Miller, A. J. Murgo, and N. P. Plotnikoff, Enkephalin-enhancement of active T-cell rosettes from lymphoma patients, Clin. Immunol. Immunopathol. 26: 446 (1983).CrossRefGoogle Scholar
  9. 9.
    D. T. Y. Yu, Human lymphocyte receptor movement induced by sheep erythrocyte binding: Effect of temperature and neuraminidase treatment, Cell Immunol. 14: 313 (1974).PubMedCrossRefGoogle Scholar
  10. 10.
    D. T. Y. Yu, J. B. Peter, H. E. Paulus, and K. M. Nies, Human lymphocyte subpopulations. Study of T and B cells and density distribution, Clin. Immunol. Immunopathol. 2: 333 (1974).CrossRefGoogle Scholar
  11. 11.
    J. Wybran and H. H. Fudenberg, Thymus-derived rosette-forming cells in various human disease states: Cancer, lymphoma, bacterial and viral infections, and other diseases, J. Clin. Investig. 52: 1026 (1972).CrossRefGoogle Scholar
  12. 12.
    E. Loumaye and K. J. Catt, Homologous regulation of gonadotropin-releasing hormone receptors in cultured pituitary cells, Science 215: 983 (1982).PubMedCrossRefGoogle Scholar
  13. 13.
    E. R. Unanue, W. D. Perkins, and M. J. Karnovsky, Ligand-induced movement of lymphocyte membrane macromolecules. I. Analysis by immunofluorescence and ultrastructural radioautography, J. Exp. Med. 136: 885 (1972).Google Scholar
  14. 14.
    G. B. Ryan, E. R. Unanue, and M. J. Karnovsky, Inhibition of surface capping of macromolecules by local anaesthetics and tranquilizers, Nature (London) 250: 56 (1974).CrossRefGoogle Scholar
  15. 15.
    A. Bernard, C. Gelin, B. Raynal, D. Pham, C. Gosse, and L. Boumsell, Phenomenon of human T-cell rosetting with sheep erythrocytes analyzed with monoclonal antibodies. “Modulation” of a partially hidden epitope determining the conditions of interaction between T-cells and erythrocytes, J. Exp. Med. 155: 1317 (1982).PubMedCrossRefGoogle Scholar
  16. 16.
    F. D. Howard, J. A. Ledbetter, J. Wong, C. P. Bieber, E. B. Stinson, and L. A. Herzenberg, A human T-lymphocyte differentiation marker defined by monoclonal antibodies that block E-rosette formation, J. Immunol. 126: 2117 (1981).PubMedGoogle Scholar
  17. 17.
    R. B. Ashman, M. F. L. LaVia, S. Sawanabori, and A. J. Nahmias, Studies on the mechanism of E-rosette formation and inhibition, Clin. Immunol. Immunopathol. 16: 39 (1980).CrossRefGoogle Scholar
  18. 18.
    W. H. West, S. M. Payne, J. L. Weese, and R. B. Herberman, Human T-lymphocyte subpopulations: Correlation between E-rosette-forming affinity and expression of the Fc receptor, J. Immunol. 119: 548 (1977).PubMedGoogle Scholar
  19. 19.
    D. T. Y. Yu, Human lymphocyte subpopulation: Early and late rosettes, J. Immunol. 115: 91 (1975).PubMedGoogle Scholar
  20. 20.
    G. Koshki, R. Streaty, and W. A. Klee, Modulation of sodium-sensitive GTPase by partial opiate agonists. An explanation for the dual requirement for Na+ and GTP in inhibitory regulation of adenylate cyclase, J. Biol. Chem. 257: 14035 (1982).Google Scholar
  21. 21.
    C. R. Kahn, Membrane receptors for hormones and neurotransmitters, J. Cell Biol. 70: 261 (1976).PubMedCrossRefGoogle Scholar
  22. 22.
    M. Bornens, E. Karsenti, and S. Avrameas, Receptor mobility and its cooperative restriction by ligands, in: “Immunology of Receptors,” B. Cinader, ed., Immunol. Series 6:41 (1977).Google Scholar
  23. 23.
    C. B. Pert, G. Pasternak, and S. H. Snyder, Opiate agonists and antagonists discriminated by receptor binding in brain, Science 182: 1359 (1973).PubMedCrossRefGoogle Scholar
  24. 24.
    E. J. Simon and J. Groth, Kinetics of opiate receptor inactivation by sulfhydryl reagents: Evidence for conformational change in presence of sodium ions, Proc. Natl. Acad. Sci. USA 72: 2402 (1975).CrossRefGoogle Scholar
  25. 25.
    E. Hazum, K.-J. Chang and P. Cuatrecasas, Role of disulphide and sulfhydryl groups in clustering of enkephalin receptors in neuroblastoma cells. Nature (London) 282: 626 (1975).CrossRefGoogle Scholar
  26. 26.
    J. J. Madden, R. M. Donahoe, I. E. Smith, D. E. Martinson, S. Moss-Wells, L. Klein, and A. Falek, Increased rate of E-rosette formation by T-lymphocytes of pregnant women who drink alcohol, Clin. Immunol. Immunopathol. 33: 67 (1984).CrossRefGoogle Scholar
  27. 27.
    R. M. Donahoe, J. K. A. Nicholson, J. J. Madden, F. Hollingsworth, A. Falek, D. A. Shafer, D. Gordon, and P. Bokos, Drug abuse, leukocyte antigenic markers, and AIDS, (submitted 1985 ).Google Scholar
  28. 28.
    R. M. Donahoe, J. J. Madden, F. Hollingsworth, D. A. Shafer, A. Falek, J. K. A. Nicholson, and P. Bokos, Immunomodulation by behaviorally active drugs provides a paradigm for connecting AIDS-like processes and psychoneuroimmunology, Proc. 1st Int. Workshop Neuroimmunol. (in press 1985).Google Scholar
  29. 29.
    W. Shain and D. O. Carpenter, Mechanisms of synaptic modulation, Int. Rev. Neurobiol. 22: 205 (1981).PubMedCrossRefGoogle Scholar
  30. 30.
    J. M. Hiller, L. M. Angel, and E. J. Simon, Multiple opiate receptors: Alcohol selectively inhibits binding to delta receptors, Science 214: 468 (1981).PubMedCrossRefGoogle Scholar
  31. 31.
    M. E. Charness, A. S. Gordon, and I. Diamond, Ethanol modulation of opiate receptors in cultured neural cells, Science 222: 1246 (1983).PubMedCrossRefGoogle Scholar
  32. 32.
    W. D. Bowen, S. Gentleman, M. Herkenham, and C. B. Pert, Interconverting p and S forms of the opiate receptor in rat striatal patches, Proc. Natl. Acad. Sci. USA 78: 4818 (1981).PubMedCrossRefGoogle Scholar
  33. 33.
    J. Schlessinger, Y. Shechter, M. C. Willingham, and I. Pastan, Direct visualization of binding, aggregation and internalization of insulin and epidermal growth factor on living fibroblast cells. Proc. Natl. Acad. Sci. USA 75: 2659 (1978).PubMedCrossRefGoogle Scholar
  34. 34.
    G. M. Edelman, Surface modulation in cell recognition and cell growth, Science 192: 218 (1976).PubMedCrossRefGoogle Scholar
  35. 35.
    R. Guillemin, T. Vargo, J. Rossier, S. Minnick, N. Ling, C. Rivier, C. Vale, and F. Bloom, 0-Endorphin and adrenocorticotropin are secreted concomitantly by the pituitary gland, Science 197: 1367 (1977).PubMedCrossRefGoogle Scholar
  36. 36.
    J. D. Sapira, J. C. Ball, and H. Penn, Causes of death among institutionalized narcotic addicts, J. Chron. Dis. 22: 733 (1970).PubMedCrossRefGoogle Scholar
  37. 37.
    R. Palacios and 0. Martinez-Maza, Is the E-receptor on human T-lymphocytes a “negative signal receptor” ?, J. Immunol. 129: 2479 (1982).PubMedGoogle Scholar
  38. 38.
    R. Mandle, R. E. Birch, S. H. Polmar, G. M. Kammer, and S. A. Rudolph, Abnormal adenosine-induced immunosuppression and cAMP metabolism in T-lymphocytes of patients with systemic lupus erythematosus, J. Immunol. 79: 7542 (1982).Google Scholar
  39. 39.
    S. C. Meuer, R. E. Hussey, M. Fabbi, M. Fox, D. Acuto, 0. Fitzgerald, K. A. Hodgdon, J. C. Protentis, S. F. Schlossman, and E. L. Reinherz, An alternate pathway of T-cell activation: A functional role for the 50 KD T11 sheep erythrocyte receptor protein, Cell 36: 897 (1984).Google Scholar
  40. 40.
    G. Semenzota, G. Basso, V. Fagiolo, A. Pezzutto, C. Agostini, M. G. Cocito, and G. Gasparotto, Active and later rosette-forming cells: Immunological and cytochemical characterization, Cell. Immunol. 64: 227 (1981).Google Scholar
  41. 41.
    M. Wilkinson and A. Morris, The E-receptor regulates interferon-gamma production: Four receptor model for human lymphocyte activation, Eur. J. Immunol. 14: 708 (1984).PubMedCrossRefGoogle Scholar
  42. 42.
    G. H. Reem and N. H. Yeh, Interleukin 2 regulates expression of its receptor and synthesis of gamma interferon by human T-lymphocytes, Science 225: 429 (1984).PubMedCrossRefGoogle Scholar
  43. 43.
    D. G. Payan, J. D. Levine, and E. J. Goetzl, Modulation of immunity and hypersensitivity by sensory neuropeptides, J. Immunol. 132: 1601 (1984).PubMedGoogle Scholar
  44. 44.
    N. S. Nadi, J. I. Nurnberger, Jr., and E. S. Gershon, Muscarinic cholinergie receptors on skin fibroblasts in familial affective disorder, New Engl. J. Med. 311: 225 (1984).Google Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • Robert Donahoe
    • 1
  • John Madden
    • 1
  • Felicia Hollingsworth
    • 1
  • David Shafer
    • 1
  • Arthur Falek
    • 1
  1. 1.Department of PsychiatryEmory University and Georgia Mental Health InstituteAtlantaGeorgia

Personalised recommendations