Endogenous Opioid Systems, Stress, and Cancer

  • Ian S. Zagon
  • Patricia J. Mclaughlin


Opium’s importance in both medicinal and social contexts dates back thousands of years (Blum, 1970; Terry and Pellens, 1928). Interest in opiates and opiate-like compounds (heretofore collectively referred to as “opioids”) had been maintained throughout the years. A major breakthrough in our understanding of opioids came with the discovery of opioid receptors in 1973 by groups led by Simon (Simon et al., 1973), Snyder (Pert and Snyder, 1973), and Terenius (1973), along with the equally elegant finding of endogenous opioids by Hughes, Kosterlitz and colleagues (Hughes, 1975; Hughes et al., 1975) in 1975. Discovery of opioid receptors and the endogenous opioids (collectively referred to as “endogenous opioid systems”) stands as a landmark of scientific achievement. Needless to say, this has stimulated intense research activity which has already culminated in important information as to the mechanisms and functions of opioids. One such exciting insight has been the discovery in 1983 that endogenous opioid systems are related to growth of both normal and abnormal cells and tissues (Zagon and McLaughlin, 1983a, b, c, d). This has led to a fascinating story concerning the fundamental nature of growth (Zagon and McLaughlin, 1984a, b, c; 1985a, b). The major purpose of this chapter is to review the evidence relating endogenous opioid systems to cancer. Since some aspects of stress may be associated with the endogenous opioid systems, and ACTH and some endogenous opioids share the same precursor (pro-opiomelanocortin), we have also included relevant information on the topic of stress and cancer in an attempt to provide perspective to the entire field of endogenous opioid systems and tumor biology.


Opioid Receptor Natural Killer Cell Activity Opioid Peptide Tumor Incidence Opiate Receptor 
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. Amano, T. Richelson, E., and Nirenberg, M., 1972, Neurotransmitter synthesis by neuroblastoma clones, Proc. Nat’l Acad. Sci., USA, 69: 258.PubMedCrossRefGoogle Scholar
  2. Andersen, N. B., 1966, The effect of CNS depressants in mitosis, Acta Anaesta Scand. Suppl., 22: 7.Google Scholar
  3. Arima, E., Byfield, J. E., Finkelstein, J. Z., and Fonkalsrud, 1973, An experimental model for the therapy of mouse neuroblastoma, J. Pediat. Surg., 8: 757.PubMedCrossRefGoogle Scholar
  4. Aylsworth, C. F., Hodson, C. A., and Meites, J., 1979, Opiate antagonists can inhibit mammary tumor growth in rats, Proc. Soc. Exp. Biol. Med., 161: 18.PubMedGoogle Scholar
  5. Blalock, J. E. and Smith, E. M., 1980, Human leukocyte interferons: structural and biological relatedness to adrenocorticotropic hormone and endorphins, Proc. Nat’l Acad. Sci., USA, 77: 5972.PubMedCrossRefGoogle Scholar
  6. Blalock, J. E. and Smith, E. M., 1981, Human leukocyte interferon (HuIFN-a): potent endorphin-like opioid activity, Biochem. Biophys. Res. Comm., 101: 472.PubMedCrossRefGoogle Scholar
  7. Blum, R. H., 1970, A history of opium, in: “Society and Drugs. I. Social and Cultural Observations,” Jossey-Bass, Inc., San Francisco.Google Scholar
  8. Blumberg, H. and Dayton, H. B., 1973, Naloxone and related compounds, in: “Agonist and Antagonist Actions of Narcotic Analgesic Drugs,” H. N. Kosterlitz, H. O. J. Collins, and J. E. Villareal, eds., Raven Press, New York.Google Scholar
  9. Blumberg, H. and Dayton, H. B., 1974, Naloxone, naltrexone and related noroxymorphones, in: “Narcotic Antagonists,” M. C. Braude, L. S. Harris, E. L. May, J. P. Smith, and J. E. Villareal, Raven Press, New York.Google Scholar
  10. Brands, M., Hirst, M., and Gowdey, C. W., 1975, Duration of analgesia in mice after heroin by two testing methods, Canad. J. Physiol. Pharmacol., 54: 381.CrossRefGoogle Scholar
  11. Brechner, T., Motyka, D., and Sherman, J., 1983, Growth enhancement of prolactin-sensitive mammary tumor by periaqueductal gray stimulation, Life Sci., 32: 525.PubMedCrossRefGoogle Scholar
  12. Brostrom, C. O., Brostrom, M. A., and Wolff, D. W., 1977, Calcium-dependent adenylate cyclase from rat cerebral cortex, J. Biol. Chem., 252: 5677.PubMedGoogle Scholar
  13. Brown, S. M., Stimmel, B., Taub, R. N., Kochwa, S., and Rosenfeld, R. E., 1974, Immunologic dysfunction in heroin addicts, Arch. Internal Med., 134: 1001.Google Scholar
  14. Brown, D. R., Blank, M. S., and Holtzman, S. G., 1980, Suppression by naloxone of water intake induced by deprivation and hypertonic saline in intact and hypophysectomized rats, Life Sci., 26: 1535.PubMedCrossRefGoogle Scholar
  15. Bruni, J. F., Van Vugt, D., Marshall, S., and Meites, J., 1977, Effects of naloxone, morphine and methionine enkephalin on serum prolactin, luteinizing hormone, follicle stimulating hormone, thyroid stimulating hormone and growth hormone, Life Sci., 21: 461.PubMedCrossRefGoogle Scholar
  16. Chang, K. J., 1984, Opioid peptides have actions on the immune system, Trends Neurosci., 7: 234.CrossRefGoogle Scholar
  17. Cherubin, C. E. and Brown, J., 1968, Systemic infections in heroin addicts, Lancet, (i):298.Google Scholar
  18. Clement-Jones, V., Corder, R., and Lowry, P. J., 1980, Isolation of human met-enkephalin and two groups of putative precursors from an adrenal medullary tumour, Biochem. Biophys. Res. Comm., 95: 665.PubMedCrossRefGoogle Scholar
  19. Dafny, N., 1983a, Interferon modifies morphine withdrawal phenomena in rodents, Neuropharmacology, 22: 647PubMedCrossRefGoogle Scholar
  20. Dafny, N., 1983b, Modification of morphine withdrawal by interferon, Life Sci., 32: 303.PubMedCrossRefGoogle Scholar
  21. D’Amato, R. and Holaday, J. W., 1984, Multiple opioid receptors in endotoxic shock: evidence for d involvement and p -8 interactions in vitro, Proc. Nat’l Acad. Sci., USA, 81: 2898.PubMedCrossRefGoogle Scholar
  22. Epstein, L. B., Rose, M. E., McManus, N. H., and Li, C. H., 1982, Absence of functional and structural homology of natural and recombinant human leukocyte interferon (IFN-a) with human a-ACTH and 8-endorphin, Biochem. Biophys. Res. Comm., 104: 341.PubMedCrossRefGoogle Scholar
  23. Faden, A. I. and Holaday, J. W., 1980, Naloxone treatment of endotoxin shock: stereospecificity of physiologic and pharmacologic effects in the rat, J. Pharmacol. Exp. Ther., 212: 441.PubMedGoogle Scholar
  24. Faith, R. E., Plotnikoff, N. P., and Murgo, A. J., Effects of opiates and enkephalins-endorphins on immune functions, NIDA Technical Meeting, Boston, in press.Google Scholar
  25. Faith, R. E., Liang, H. J., Murgo, A. J., and Plotnikoff, N. P., 1984, Neuroimmunomodulation with enkephalins: enhancement of natural killer (NK) cell activity in vitro, Clin. Immunol. Immunopathol., 31: 412.PubMedCrossRefGoogle Scholar
  26. Falek, A. and Hollingsworth, F., 1980, Heroin and chromosome damage, Arch, gen. Psychiat., 37: 227.CrossRefGoogle Scholar
  27. Finkelstein, J. Z., Arima, E., Byfield, P. E., Byfield, J. E., and Fonkalsrud, E. W., 1973, Murine neuroblastoma: a model of human disease, Canc. Chemother, Rep., 57: 405.Google Scholar
  28. Fischer, E. G. and Falke, N. E., 1984, I3-endorphin modulates immune Functions - a review, Proc. of VIIth World Congress Intern. College of Psychosomatic Med.Google Scholar
  29. Fischman, H. K., Roizin, L., Moralshoili, E., Joy, C., and Rainer, J. D., 1977, Effects of prolonged administration of “street heroin” on the chromosomes of Macaca mulatti (Rheses) monkeys, in: “Neurotoxicology”, L. Roizin, H. Shirakii and N. Grecevic, Raven Press, New York.Google Scholar
  30. Frey, E. A. and Krebabian, J. W., 1984, A u-opiate receptor in 7315c tumor tissue mediates inhibition of immunoreceactive prolactin release and adenvlate cyclase activity, Endocrinology, 115: 1797.PubMedCrossRefGoogle Scholar
  31. Gayton, R. J., Lambert, L. A., and Bradley, P. B., 1978, Failure of (+)naloxone to antagonize responses to opioid peptides, Neuropharmacology, 17: 549.PubMedCrossRefGoogle Scholar
  32. Geber, W. F. and Schramm, L. C., 1975, Congenital malformations of the central nervous system produced by narcotic analgesics in the hamster, Am. J. Obstet. Gynec., 123: 705.PubMedGoogle Scholar
  33. Geber, W. F., Lefkowitz, S. S., and Hung, C. Y., 1975, Effect of morphine, hydromorphine, methadone, mescaline, trypan blue, vitamin A, sodium salicylate, and caffeine on the serum interferon level in response to viral infection, Arch. Int. Pharmacodyn, 214: 322.PubMedGoogle Scholar
  34. Geber, W. F., Lefkowitz, S. S., and Hung, C. Y., 1976, Action of naloxone on the interferon-lowering activity of morphine in the mouse, Pharmacology, 14: 322.PubMedCrossRefGoogle Scholar
  35. Gershbein, L. I., Benuck, I., and Shurrager, P. S., 1974, Influence of stress on lesion growth and on survival of animals bearing parenteral and intracerebral leukemia L1210 and Walker tumors, Oncology, 30: 429.PubMedCrossRefGoogle Scholar
  36. Giering, J. E., Davidson, T. A., Shetty, B. V., and Truant, A. P., 1974, in: “Narcotic Antagonists,” M. C. Braude, L. S. Harris, E. L. May, J. P. Smith, and J. E. Villarreal, ed., Raven Press, New York.Google Scholar
  37. Gilman, S. C., Schwartz, J. M., Miller, R. J., Bloom, F. E., and Feldman, J. D., 1982, 0-endorphin enhances lymphocyte proliferative responses, Proc. Nat’l Acad. Sci., USA, 79: 4226.Google Scholar
  38. Güngör, M., Gene, E., Sugduyu, H., Eroglu, L., and Koyuncuoglu, H., 1980, Effect of chronic administration of morphine on primary immune response in mice, Experientia, 36: 1309.PubMedCrossRefGoogle Scholar
  39. Harpel, H. S. and Gautieri, R. F., 1968, Morphine-induced fetal malformations, J. Pharm. Sci., 57: 1590.PubMedCrossRefGoogle Scholar
  40. Hazum, E., Chang, K.-J. and Cuatrecasas, P., 1979, Specific nonopiate receptors for ß-endorphin, Science, 205: 1033.PubMedCrossRefGoogle Scholar
  41. Ho, W.K.K. and Leung, A., 1979, Effects of morphine addiction on concanavalin A-mediated blastogenesis, Pharmacol. Res. Comm., 11: 413.Google Scholar
  42. Hughes, J., 1975, Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine, Brain Res., 88: 295.PubMedCrossRefGoogle Scholar
  43. Hughes, J. A., Smith, T. W., Kosterlitz, H. W., Fothergill, L. A., Morgan, B. A., and Morris, H. R., 1975, Identification of two pentapeptides from the brain with potent opiate agonist activity, Nature, 258: 577.PubMedCrossRefGoogle Scholar
  44. Hui, F. W., Krikun, E., Hirsh, E. M., Blaiklock, R. G., and Smith, A. A., 1976, Inhibition of nucleic acid synthesis in the regenerating limb of salamanders treated with dl-methadone or narcotic antagonists, Exp. Neurol., 53: 267.PubMedCrossRefGoogle Scholar
  45. Hung, C. Y., Lefkowitz, S. S., and Geber, W. F., 1973, Interferon inhibition by narcotic analgesics, Proc. Soc. Exp. Biol. Med., 142: 106.PubMedGoogle Scholar
  46. Hussey, H. H. and Katz, S., 1950, Infections resulting from narcotic addiction: report of 102 cases, Am. J. Med., 9: 186.PubMedCrossRefGoogle Scholar
  47. Iijima, I., Minamikawa, J., Jacobson, A.E., Brossi, A., and Rice, K.C., 1978, Studies in the (+)-morphinan series.5. Synthesis and biological properties of (+)-naloxone, J. Med. Chem., 21: 398.PubMedCrossRefGoogle Scholar
  48. Inoue, N., and Hatankaka, H., 1982, Nerve growth factor induces specific enkephalin binding sites in a nerve cell line, J. Biol. Chem., 257: 9238.PubMedGoogle Scholar
  49. Ito, H. and Hidaka, H., 1983, Antitumor effect of a calmodulin antagonist on the growth of solid sarcoma-180, Cancer Lett., 19: 215.PubMedCrossRefGoogle Scholar
  50. Jaffe, E. H. and Martin, W. R., 1980, Narcotic analgesics and antagonists, in: “The Pharmacologic Basis of Therapeutics,” L. S. Goodman and A. Gilman, eds., MacMillan Publ. Co., New York, p. 494.Google Scholar
  51. Jasinski, D. R., Martin, W. R., and Haertzen, C. A., 1967, The human pharmacology and abuse potential of N-allylnoroxymorphone (naloxone), J. Pharmacol. Exp. Ther., 159: 420.Google Scholar
  52. Johnson, H. M., Smith, E. M., Torres, B. A., and Blalock, J. E., 1982, Regulation of the in vitro antibody response by neuroendocrine hormones, Proc. Nat’l Acad. Sci., USA 79: 4171.PubMedCrossRefGoogle Scholar
  53. Jörnvall, H., Persson, M., and Ekman, R., 1982, Structural comparisons of leukocyte interferon and pro-opiomelanocortin correlated with immunological similarities, FEBS Letters, 137: 153.PubMedCrossRefGoogle Scholar
  54. Klee, W. A. and Nirenberg, M., 1974, A neuroblastoma x glioma hybrid cell line with morphine receptors, Proc. Nat’l Acad. Sci., USA, 71: 3474.PubMedCrossRefGoogle Scholar
  55. Lahti, R. A. and Collins, R. J., 1978, Chronic naloxone results in prolonged increases in opiate binding sites in brain, Eur. J. Pharmacol., 51: 185.PubMedCrossRefGoogle Scholar
  56. Lampert, A., Nirenberg, M., and Klee, W. A., 1976, Tolerance and dependence evoked by an endogenous opiate peptide, Proc. Nat’l Acad. Sci., USA 73: 3165.PubMedCrossRefGoogle Scholar
  57. Lee, S.-C. and Lin, J.-H., 1975, An inhibitory effect of acupuncture on the growth of Ehrlich ascites tumor cells in mice, Chinese Med. J. 22: 167.Google Scholar
  58. Lefkowitz, S. S. and Chiang, C. Y., 1975, Effects of certain abused drugs on hemolysin forming cells, Life Sci., 17: 1763.PubMedCrossRefGoogle Scholar
  59. Lefkowitz, S. S. and Nemeth, D., 1976, Immunosuppression of rosette-forming cells, Adv. Exp. Med. Biol., 733: 269.CrossRefGoogle Scholar
  60. LeShan, L. L., 1959, Psychological states as factors in the development of malignant disease: a critical review, J. Nat. Cancer Inst., 22:1. Lewis, J. W., Cannon, J. T., and Leibeskind, J. C., 1980, Opioid and nonopioid mechanisma of stress analgesia, Science, 208: 623.Google Scholar
  61. Lewis, J. W., Shavit, Y., Terman, G. W., Nelson, L. R., Gale, R. P., and Liebeskind, J. C., 1983a, Apparent involvement of opioid peptides in stress-induced enhancement of tumor growth, Peptides, 4: 635.PubMedCrossRefGoogle Scholar
  62. Lewis, J. W., Shavit, Y., Terman, G. W., Gale, R. P., and Liebeskind, J. C., 1983b, Stress and morphine affect survival of rats challenged with a mammary ascites tumor (MAT 13762B), Nat. Immun. Cell Growth Regul., 3: 43.PubMedGoogle Scholar
  63. Lopker, H., Abood, L. G., Hoss, W., and Lionetti, F. J., 1980, Stereo-selective muscarinic acetylcholine and opiate receptors in human phagocytic leukocytes, Biochem. Pharm., 29: 1361.PubMedCrossRefGoogle Scholar
  64. Lord, J. A. H., Waterfield, A. A., Huges, J., and Kosterlitz, H. W., 1977, Endogenous opioid peptides: multiple agonists and receptors, Nature, 267: 495.PubMedCrossRefGoogle Scholar
  65. Ma, W. C., 1931, A cytological study of acute and chronic morphinism in albino rat, Clin. J. Physiol., 5: 251.Google Scholar
  66. Martin. W. R., Eades, C. G., Thompson, J. A., Huppler, R. E., and Gilbert, P. E., 1976, The effects of morphine and nalorphine-like drugs in the non-dependent and morphine-dependent chronic spinal dog, J. Pharmacol. Exp. Ther., 197: 517.Google Scholar
  67. Matthews, P. M., Froelich, C. J., Sibbitt, W. L., and Bankhurst, A. D., 1983, Enhancement of natural cytotoxicity by I3-endorphin, J. Immunol., 130: 1658.Google Scholar
  68. McCain, H. W., Lamster, I. B., Bozzone, J. M., and Grbic, J. T., 1982, fi-endorphin modulates human immune activity via-non-opiate receptor mechanisma, Life Sci., 31: 1619.Google Scholar
  69. McDonough, R. J., Madden, J. L., Falek, A., Shafer, D. A., Pline, M., Gordon, D., Bokos, P., Keuhule, J. C., and Mendelson, J., 1980, 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.PubMedGoogle Scholar
  70. McLaughlin, P. J. and Zagon, I. S., 1984, Opioid regulation of tumor cell growth in vitro, Soc. Neurosci., 14th Annual Meeting, 10: 111.Google Scholar
  71. Miller, G. C., Murgo, A. J., and Plotnikoff, N. P., 1983, Enkephalinsenhancement of active T-cell rosettes from lymphoma patients, Clin. Immunol., Immunol., Immunopathol., 26: 446.CrossRefGoogle Scholar
  72. Miller, G. C., Murgo, A. J., and Plotnikoff, N. P., 1984, Enkephalinsenhancement of active T-cell rosettes from normal volunteers, Clin. Immunol. Immunopath., 31: 132.CrossRefGoogle Scholar
  73. Newberry, B. H., Frankie, G., Beatty, P. A., Maloney, B. D., and Gilchrist, J. C., 1972, Shock stress and DMBA-induced mammary tumors, Psychosom. Med., 34: 295.PubMedGoogle Scholar
  74. North-Root, H., Martin, D. W., and Toliver, A. P., 1976, Binding of an opiate, levorphanol, to intact neuroblastoma cells in continuous culture, Physiol. Chem. Physics, 8: 221.Google Scholar
  75. Osamura, R. Y., Watanabe, K., Yoshimasa, T., Nakao, K., and Imura, H., 1984, Immunohistochemical localization of met-enkephalin, met enkephalin-arg6-gly7-leu8, met-enkephalin-arg6-phe7 and leuenkephalin in human adrenal medulla and pheochromocytomas, Peptides 5: 993.PubMedCrossRefGoogle Scholar
  76. Perrin, G. M. and Pierce, I. R., 1959, Psychosomatic aspects of cancer, Psychosom. Med., 21: 397.PubMedGoogle Scholar
  77. Pert, G. B. and Snyder, S. H., 1973, Opiate receptor: demonstration in nervous tissue, Science, 179: 1011.PubMedCrossRefGoogle Scholar
  78. Plotnikoff, N. P. and Miller, G. C., 1983, Enkephalins as immuriomodulators, Int. J. Immunopharmacol., 5: 437.PubMedCrossRefGoogle Scholar
  79. Plotnikoff, N. P., Miller, G. C., and Murgo, A. J., 1982, Enkephalinsendorphins: immunomodulators in mice, Int. J. Immunopharmacol., 4: 366.CrossRefGoogle Scholar
  80. Plotnikoff, N. P., Murgo, A. J., Miller, G. C., Corder, C. N., and Faith, R. E., 1985, Enkephalins: immunomodulators, Fed. Proc., 44: 118.PubMedGoogle Scholar
  81. Portoghese, P. S., Larson, D. L., Sayre, L. M., Fries, D. S., and Takemori, A. E., 1980, A novel opiate receptor site directed alkylating agent with irreversible narcotic antagonistic and reversible agonistic activities, J. Med. Chem., 23: 233.PubMedCrossRefGoogle Scholar
  82. Pradhan, S. N. and Ray, P., 1974, Effects of stress on growth of transplanted and 7, 12-dimethylbenz(a)anthracene-induced tumors and their modification by psychotropic drugs, JNCI, 53: 1241.PubMedGoogle Scholar
  83. Rashkis, H. A., 1952, Systemic stress as an inhibitor of experimental tumors in Swiss mice, Science, 116: 169.PubMedCrossRefGoogle Scholar
  84. Recant, L., Voyles, N. R., Luciano, M., and Pert, C. B., 1980, Naltrexone reduces weight gain, alters “ß-endorphin”, and reduces insulin output from pancreatic islets of genetically obese mice, Peptides, 1: 309.PubMedCrossRefGoogle Scholar
  85. Riley, V., 1981, Psychoneuroendocrine influences on immunocompetence and neoplasia, Science, 212: 1100.PubMedCrossRefGoogle Scholar
  86. Sano, M. and Kitajima, S., 1983, Ontogeny of calmodulin and calmodulindependent adenylate cyclase in rat brain, Dey. Brain Res., 7: 215.CrossRefGoogle Scholar
  87. Sawynok, J., Pinsky, C., and LaBella, F. S., 1979, Mini-review on the specificity of naloxone as an opiate antagonist, Life Sci., 25: 1621.PubMedCrossRefGoogle Scholar
  88. Schweigerer, H., Bhakdi, S., and Teschemacher, H., 1982, Specific nonopiate binding sites for human ß-endorphin on the terminal complex of human complement, Nature, 296: 572.PubMedCrossRefGoogle Scholar
  89. Seifter, E., Rettura, G., Zisblatt, M., Levenson, S. M., Levine, N., Davidson, A., and Seifter, J., 1973, Enhancement of tumor development in physically stressed mice inoculated with an oncogenic virus, Experientia, 29: 1379.PubMedCrossRefGoogle Scholar
  90. Sharma, S. K., Klee, W. A., and Nirenberg, M., 1975a, Dual regulation of adenylate cyclase accounts for narcotic dependence and tolerance, Proc. Nat’l Acad. Sci., USA, 72: 3092.PubMedCrossRefGoogle Scholar
  91. Sharma, S. K., Klee, W. A., and Nirenberg, M., 1975b, Opiate-dependent modulation of adenylate cyclase, Proc. Nat’l Acad. Sci., USA, 74: 3365.CrossRefGoogle Scholar
  92. Shavit, Y., Lewis, J. W., Terman, G. W., Gale, R. P., Liebeskind, J.C., 1983, Endogenous opioids may mediate the effects of stress on tumor growth and immune function, Proc. West. Pharmacol. Soc., 26: 53.PubMedGoogle Scholar
  93. Shavit, Y., Lewis, J. W., Terman, G. W., Gall, R. P., and Liebeskind, J. C., 1984, Opioid peptides mediate the suppressive effect of stress on natural killer cell cytotoxicity, Science, 223: 188.PubMedCrossRefGoogle Scholar
  94. Simantov, R., Nadler, H., and Levy, R., 1982, A genetic approach to reveal the action of the opiate receptor in selected neuroblastoma-glioma cells. Interaction with a-adrenoreceptors, calmodulin and calcium ion ATPase, Eur. J. Biochem., 128: 461.PubMedCrossRefGoogle Scholar
  95. Simon, E. J., 1964, Inhibition of bacterial growth by drugs of the morphine series, Science, 144: 543.PubMedCrossRefGoogle Scholar
  96. Simon, E. J., 1971, Single cells, in: “Narcotic Drugs,” D. H. Clouet, ed., Plenum Press, New York.Google Scholar
  97. Simon, E. J., Miller, J. M., and Edelman, I., 1973, Stereospecific binding of the potent narcotic analgesic (3H)etorphine to rat brain homogenate, Proc. Nat’l Acad. Sci., USA, 70: 1947.PubMedCrossRefGoogle Scholar
  98. Simon, R. H., Lovett, E. J., Tomaszek, D., and Lundy, J., 1980, Electrical stimulation of the midbrain mediates metastatic tumor growth, Science, 209: 1132.PubMedCrossRefGoogle Scholar
  99. Simon, R. H., Arbo, T. E., and Lundy, J., 1984, 8-endorphin injected into the nucleus of the raphe magnus facilitates metastatic tumor growth, Brain Res. Bull., 12: 487.Google Scholar
  100. Sinatra, R. A., Milks, L. C., and Ford,D. H., 1978, Structural alterations in normal and axotomized facial nucleus neurons after treatment with morphine, Experientia, 35: 1218.CrossRefGoogle Scholar
  101. Singh, V. K., Jakubovic, A., and Thomas, D. A., 1980, Suppressive effects of methadone on human blood lymphocytes, Immunol. Lett., 2: 177.CrossRefGoogle Scholar
  102. Sklar, L. S. and Anisman, H., 1979, Stress and coping factors influence tumor growth, Science, 205: 513.PubMedCrossRefGoogle Scholar
  103. Sklar, L. S. and Anisman, H., 1980, Social stress influences tumor growth, Psychosom. Med., 42: 347.PubMedGoogle Scholar
  104. Sklar, L. S. and Anisman, H., 1981, Stress and cancer, Psychol. Bull., 89: 369.PubMedCrossRefGoogle Scholar
  105. Sotkin, T. A., Seidler, F. J., and Whitmore, W. L., 1980, Effects of maternal methadone administration on ornithine decarboxylase in brain and heart of the offspring: relationships of enzyme activity to dose and to growth impairment in the rat, Life Sci., 26: 861.CrossRefGoogle Scholar
  106. Smith, E. M. and Blalock, J. E., 1981, Human lymphocyte production of corticotropin and endorphin-like substances: association with leukocyte interferon, Proc. Nat’l Acad. Sci., USA, 78: 7530.CrossRefGoogle Scholar
  107. Sullivan, S. N., Bloom, S. R., and Polak, J. M., 1978, Enkephalin in peripheral neuroendocrine tumours, Lancet, 1: 986.PubMedCrossRefGoogle Scholar
  108. Takemori, A. E. and Portoghese, P. S., 1985, Affinity labels for opioid receptors, Ann. Rev. Pharmacol., in press.Google Scholar
  109. Takemori, A. E., Larson, D. L., and Portoghese, P. S., 1981, The irreversible narcotic antagonistic and reversible agonistic properties of the fumarate methyl ester derivative of naltrexone, Eur. J. Pharmacol., 70: 445.PubMedCrossRefGoogle Scholar
  110. Tang, A. H. and Collins, R. J., 1978, Enhanced analgesic effects of morphine after chronic administration of naloxone in the rat, Eur. J. Pharmacol., 47: 473.PubMedCrossRefGoogle Scholar
  111. Terenius, L., 1973, Stereospecific interaction between narcotic analgesics and a synaptic plasma membrane fraction of rat cerebral cortex, Acta Pharmacol. Toxicol., 32: 317.CrossRefGoogle Scholar
  112. Terry, C. E. and Pellens, M., 1970, Pathology-tolerance-dependencewithdrawal, in: “The Opium Problem,” C. E. Terry and M. Pellens, eds., Patterson Smith Publishing Corp., New York.Google Scholar
  113. Thompson, C. I., Kreider, J. W., Black, P. L., Schmidt, T. J., and Margules, D. L., 1983, Genetically obese mice: resistance to metastasis of B16 melanoma and enhanced T-lymphocyte mitogenic responses, Science, 220: 1183.PubMedCrossRefGoogle Scholar
  114. Tubaro, E., Borelli, G., Croce, C., Cavallo, G., and Santiangeli, C., 1983, Effect of morphine on resistance to infection, J. Infectious Dig, 148: 656.CrossRefGoogle Scholar
  115. Van Epps, E. E. and Saland, L., 1984, 8-endorphin and met-enkephalin stimulate human peripheral blood mononuclear cell chemotaxis, J. Immunol., 132: 3046.Google Scholar
  116. Visintainer, M. A., Volpicelli, J. R., Seligman, N. E. P., 1982, Tumor rejection in rats after inescapable or escapable shock, Science, 216: 437.PubMedCrossRefGoogle Scholar
  117. Ward, S. J. and Takemori, A. E., 1983, Relative involvement of mu, kappa, and delta receptor mechanisms in opiate-mediated antinociception in mice, J. Pharmacol. Exp. Ther., 224: 525.PubMedGoogle Scholar
  118. Ward, S. J., Portoghese, P. S., and Takemori, A. E., 1982a, Pharmacological profiles of 8-funaltrexamine (8-FNA) and 8-chlornaltrexamine (8-CNA) on the mouse vas deferens preparation, Eur. J. Pharmacol., 80: 377.PubMedCrossRefGoogle Scholar
  119. Ward, S. J., Portoghese, P. S., and Takemori, A. E., 1982b, Pharmacological characteristics in vivo of the novel opiate 8-funaltrexamine, J. Pharmacol. Exp. Ther., 220: 494.PubMedGoogle Scholar
  120. Way, E. L., Kemp, J. W., Young, J. M., and Grassetti, D. R., 1960, The pharmacologic effects of heroin in relationship to its rate of biotransformation, J. Pharmacol. Exp. Ther., 129: 144.PubMedGoogle Scholar
  121. Weber, R. J. and Pert, C. B., 1984, Opiatergic modulation of the immune system, in: Central and Peripheral Endorphins: Basic and Clinical Aspects, E. E. Muller and A. R. Genazzini, ed., Raven Press, NY, p. 35.Google Scholar
  122. Wybran, J., 1985, Enkephalins, endorphins, substance P and the immune system, in:Neural Modulation of Immunity, R. Guillemin, M. Cohn, and T. Melnechuk, eds., Raven Press, NY, p. 157.Google Scholar
  123. Wybran, J., Appelboom, T., Famaey, J.-P., and Govaerts, A., 1979, Suggestive evidence for receptors for morphine and methionineenkephalin on normal human blood T lymphocytes, J. Immunol., 123: 1068.PubMedGoogle Scholar
  124. Yamasaki, Y., Shimamura, O., Kizu, A., Nakazawa, M., and Ijichi, H., 1983, Interactions of morphine with PGE isoproterenal, dopamine and aminophylline in rat mast cells: their effect on IgE-mediated 14Cserotonin release, Agents and Actions, 13: 21.PubMedCrossRefGoogle Scholar
  125. Zagon, I. S. and McLaughlin, P. J., 1977, The effects of different schedules of methadone treatment on rat brain development, Exp. Neurol., 56: 538.PubMedCrossRefGoogle Scholar
  126. Zagon, I. S. and McLaughlin, P. J., 1978, Perinatal methadone exposure and brain development: a biochemical study, J. Neurochem., 31: 49.PubMedCrossRefGoogle Scholar
  127. Zagon, I. S. and McLaughlin, P. J., 1981a, Heroin prolongs survival time and retards tumor growth in mice with neuroblastoma, Brain Res. Bull., 7: 25.PubMedCrossRefGoogle Scholar
  128. Zagon, I. S. and McLaughlin, P. J., 1981b, Naloxone prolongs survival time or mice treated with neuroblastoma, Life Sci., 28: 1095.PubMedCrossRefGoogle Scholar
  129. Zagon, I. S. and McLaughlin, P. J., 1983a, Naltrexone modulates tumor response in mice with neuroblastoma, Science, 221: 671.PubMedCrossRefGoogle Scholar
  130. Zagon, I. S. and McLaughlin, P. J., 1983b, Increased brain size and cellular content in infant rats treated wtih an opiate antagonist, Science, 221: 1179.PubMedCrossRefGoogle Scholar
  131. Zagon, I. S. and McLaughlin, P. J., 1983c, Naltrexone modulates growth in infant rats, Life Sci., 33: 2449.PubMedCrossRefGoogle Scholar
  132. Zagon, I. S. and McLaughlin, P. J., 1983d, Opioid antagonists inhibit the growth of metastatic murine neuroblastoma, Cancer Lett., 21: 89.PubMedCrossRefGoogle Scholar
  133. Zagon, I. S. and McLaughlin, P. J., 1984a, Duration of opiate receptor blockade determines tumorigenic response in mice with neuroblastoma: a role for endogenous opioid systems in cancer, Life Sci., 35: 409.PubMedCrossRefGoogle Scholar
  134. Zagon, I. S. and McLaughlin, P. J., 1984b, Naltrexone modulates body and brain development in rats: a role for endogenous opioids in growth, Life Sci., 35: 2057.PubMedCrossRefGoogle Scholar
  135. Zagon, I. S. and McLaughlin, P. J., 1984c, Opiates alter tumor cell growth and differentiation in vitro, NIDA Res. Monog., 49: 344.Google Scholar
  136. Zagon, I. S. and McLaughlin, P. J., 1984d, An overview of the neurobehavioral sequelae of perinatal opioid exposure, in: Neurobehavioral Teratology, J. Yanai, ed., Elsevier Science Publishers, Amsterdam.Google Scholar
  137. Zagon, I. S. and McLaughlin, P. J., 1985a, Opiate antagonist induced regulation of organ development, Physiol. Behay., in press.Google Scholar
  138. Zagon, I. S. and McLaughlin, P. J., 1985b, Naltrexone’s influence on neurobehavioral development, Pharmacol. Biochem. Behay., in press.Google Scholar
  139. Zagon, I. S., McLaughlin, P. J., Weaver, D. J., and Zagon E., 1982, Opiates, endorphins and the developing organism: a comprehensive bibliography, Neurosci. Biobehay. Rev., 6: 439.CrossRefGoogle Scholar
  140. Zagon, I. S., McLaughlin, P. J., and Zagon, E., 1984, Opiates, endorphins, and the developing organism: a comprehensive bibliography, 1982–1983, Neurosci. Biobehay. Rev., 8: 387.CrossRefGoogle Scholar
  141. Zagon, I. S. and Schengrund, C.-L., 1978, Neuronal and non-neuronal properties of neuroblastoma cells, Exp. Cell Res., 114: 159.PubMedCrossRefGoogle Scholar
  142. Zukin, R. S. and Zukin, S. R., 1981, Minireview: multiple opiate receptors: emerging concepts, Life Sci., 29: 2681.PubMedCrossRefGoogle Scholar
  143. Zukin, R. S. and Zukin, S. R., 1984, The case for multiple opiate receptors, Trends Neurosci., 7: 160.CrossRefGoogle Scholar
  144. Zukin, R. S., Sugarman, J. R., Fitz-Syage, M. L., Gardner, E. L., Zukin S. R., and Gintzler, A. R., 1982, Naltrexone-induced opiate receptor supersensitivity, Brain Res., 245: 285.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • Ian S. Zagon
    • 1
  • Patricia J. Mclaughlin
    • 1
  1. 1.Department of Anatomy and Cancer Research Center The Milton S. Hershey Medical CenterThe Pennsylvania State UniversityHersheyUSA

Personalised recommendations