Possible Physiological Roles of the Enkephalins and Endorphins

  • H. W. Kosterlitz


In the evaluation of the possible physiological roles of new neurotransmitters or neuromodulators, it is necessary to understand the mechanisms underlying their biosynthesis, release and metabolism, and interactions with their receptors. There is now a considerable amount of information on these aspects with regard to the endogenous opioid peptides, which has recently been reviewed from the basic and clinical points of view (Kosterlitz & McKnight, 1980, 1981). For this reason, it is intended to deal in this paper mainly with those concepts that are important for an understanding of the principles governing the possible physiological functions of the enkephalins and endorphins.


Growth Hormone Dorsal Horn Opioid Peptide Opiate Receptor Endogenous Opioid Peptide 
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. Akil, H., Richardson, D. E., Barchas, J. D. & Li, C. H. (1978a). Appearance of β-endorphin-like immunoreactivity in human ventricular cerebrospinal fluid upon analgesic electrical stimulation. Proc. Nat. Acad. Sci. USA, 75, 5170–5172.PubMedCentralPubMedCrossRefGoogle Scholar
  2. Akil, H., Richardson, D. E., Hughes, J. & Barchas, J. D. (1978b). Enkephalin-like material elevated in ventricular cerebrospinal fluid of pain patients after analgetic focal stimulation. Science, 201, 463–465.PubMedCrossRefGoogle Scholar
  3. Akil, H., Watson, S. J., Barchas, J. D. & Li, C. H. (1979). β-endorphin immunoreactivity in rat and human blood: radioimmunoassay, comparative levels and physiological alterations. Life Sci., 24, 1659–1666.PubMedCrossRefGoogle Scholar
  4. Akil, H., Watson, S. J., Sullivan, S. & Barchas, J. D. (1978c). Enkephalin-like material in normal human CSF: measurement and levels. Life Sci., 23, 121–126.PubMedCrossRefGoogle Scholar
  5. Almay, B. G. L., Johansson, F., von Knorring, L., Terenius, L. & Wahlström, A. (1978). Endorphins in chronic pain. I. Differences in CSF endorphin levels between organic and psychogenic pain syndromes. Pain, 5, 153–162.PubMedCrossRefGoogle Scholar
  6. Arndt, J. O. & Freye, E. (1979). Opiate antagonist reverses the cardiovascular effects of inhalation anaesthesia. Nature, 277, 399–400.PubMedCrossRefGoogle Scholar
  7. Atweh, S. F. & Kuhar, M. J. (1977a). Autoradiographic localization of opiate receptors in rat brain. I. Spinal cord and lower medulla. Brain Res., 124, 53–67.PubMedCrossRefGoogle Scholar
  8. Atweh, S. F. & Kuhar, M. J. (1977b). Autoradiographic localization of opiate receptors in rat brain. II. The brain stem. Brain Res., 129, 1–12.PubMedCrossRefGoogle Scholar
  9. Atweh, S. F. & Kuhar, M. J. (1977c). Autoradiographic localization of opiate receptors in rat brain. III. The telencephalon. Brain Res., 134, 393–405.PubMedCrossRefGoogle Scholar
  10. Austen, B. M., Smyth, D. G. & Snell, C. R. (1977). γ endorphin, a endorphin and Metenkephalin are formed extracellularly from lipotropin C fragment. Nature, 269, 619–621.PubMedCrossRefGoogle Scholar
  11. Barclay, R. K. & Phillips, M. A. (1978). Inhibition of the enkephalin degradation of leuenkephalin by puromycin. Biochem. Biophys. Res. Commun., 81, 1119–1123.PubMedCrossRefGoogle Scholar
  12. Beaumont, A., Dell, A., Hughes, J., Malfroy, B. & Morris, H. R. (1980). Studies on possible precursors for the enkephalins. In Endogenous and Exogenous Opiate Agonists and Antagonists, ed. Way, E. L. pp. 209–212. New York: Pergamon Press.CrossRefGoogle Scholar
  13. Belenky, G. L. & Holaday, J. W. (1979). The opiate antagonist naloxone modifies the effects of electroconvulsive shock (ECS) on respiration, blood pressure and heart rate. Brain Res., 177, 414–417.PubMedCrossRefGoogle Scholar
  14. Belluzzi, J. C. & Stein, L. (1977). Enkephalin may mediate euphoria and drive-reduction reward. Nature, 266, 556–558.PubMedCrossRefGoogle Scholar
  15. Bisset, G. W., Chowdrey, H. S. & Feldberg, W. (1978). Release of vasopressin by enkephalin. Brit. J. Pharmac., 62, 370–371.CrossRefGoogle Scholar
  16. Bläsig, J., Bäuerle, U. & Herz, A. (1979). Endorphin-induced hyperthermia: characterization of the exogenously and endogenously induced effects. Naunyn-Schmiedeberg’s Arch. Pharmac., 309, 137–143.CrossRefGoogle Scholar
  17. Bolme, P., Fuxe, K., Agnati, L. F., Bradley, R. & Smythies, J. (1978). Cardiovascular effects of morphine and opioid peptides following intracisternal administration in chloralose-anaesthetized rats. Eur. J. Pharmac., 48, 319–324.CrossRefGoogle Scholar
  18. Browne, R. G., Derrington, D. C. & Segal, D. S. (1979). Comparison of opiate- and opioid-peptide-induced immobility. Life Sci., 24, 933–942.PubMedCrossRefGoogle Scholar
  19. Burbach, J. P. H, Loeber, J. G., Verhoef, J., Wiegant, V. M., de Kloet, E. R. & de Wied, D. (1980). Selective conversion of γ-endorphin into peptides related to γ-and α-endorphin. Nature, 283, 96–97.PubMedCrossRefGoogle Scholar
  20. Chang, K.-J., Cooper, B. R., Hazum, E. & Cuatrecasas, P. (1979). Multiple opiate receptors: different regional distribution in the brain and differential binding of opiates and opioid peptides. Mol. Pharmac., 16, 91–104.Google Scholar
  21. Chang, W.-C., Jagannadha Rao, A. & Li, C. H. (1978). Rate of disappearance of human γ-lipotropin and γ-endorphin in adult male rats as estimated by radioimmunoassay. Int. J. Peptide Protein Res., 11, 93–94.CrossRefGoogle Scholar
  22. Cicero, T. J., Schainker, B. A. & Meyer, E. R. (1979). Endogenous opioids participate in the regulation of the hypothalamic-pituitary-luteinizing hormone axis and testosterone’s negative feedback control of luteinizing hormone. Endocrinology, 104, 1286–1291.PubMedCrossRefGoogle Scholar
  23. Clement-Jones, V., Lowry, P. J., Rees, L. H. & Besser, G M. (1980). Met-enkephalin circulates in human plasma. Nature, 283, 295–297.PubMedCrossRefGoogle Scholar
  24. Corbett, A. D., Sosa, R. P., McKnight, A. T. & Kosterlitz, H. W. (1980). Effects of electrical stimulation on the enkephalins in guinea-pig small intestine. Eur. J. Pharmac., in press.Google Scholar
  25. Csontos, K., Rust, M., Höllt, V., Mahr, W., Kromer, W. & Teschemacher, H. J. (1979). Elevated plasma γ-endorphin levels in pregnant women and their neonates. Life Sci., 25, 835–844.PubMedCrossRefGoogle Scholar
  26. Cusan, L., Dupont, A., Kledzik, G. S., Labrie, F., Coy, D. H. & Schally, A. V. (1977). Potent prolactin and growth hormone releasing activity of more analogues of met-enkephalin. Nature, 268, 544–547.PubMedCrossRefGoogle Scholar
  27. Duggan, A. W., Griersmith, B. T., Headley, P. M. & Hall, J. G (1979). Lack of effect by substance P at sites in the substantia gelatinosa where Met-enkephalin reduces the transmission of nociceptive impulses. Neurosci. Lett., 12, 313–317.PubMedCrossRefGoogle Scholar
  28. Duggan, A. W., Hall, J. G & Headley, P. M. (1977). Enkephalins and dorsal horn neurones of the cat: effects on responses to noxious and innocuous skin stimuli. Brit. J. Pharmac., 61, 399–408.CrossRefGoogle Scholar
  29. Dupont, A., Cusan, L., Garon, M., Alvarado-Urbina, G & Labrie, F. (1977). Extremely rapid degradation of [3H]-methionine-enkephalin by various rat tissues in vivo and in vitro. Life Sci., 21, 907–914.PubMedCrossRefGoogle Scholar
  30. Enjalbert, A., Ruberg, M., Arancia, S., Priam, M. & Kordon, C. (1979). Endogenous opiates block dopamine inhibition of prolactin secretion in vitro. Nature, 280, 595–597.PubMedCrossRefGoogle Scholar
  31. Faden, A. I. & Holaday, J. W. (1979). Opiate antagonists: a role in the treatment of hypovolemic shock. Science, 205, 317–318.PubMedCrossRefGoogle Scholar
  32. Firemark, H. M. & Weitzman, R. E. (1979). Effects of γ-endorphin, morphine and naloxone on\ arginine vasopressin secretion and the electroencephalogram. Neuroscience, 4, 1895–1902.PubMedCrossRefGoogle Scholar
  33. Foley, K. M., Kourides, I. A., Inturrissi, C. E., Kaiko, R. F., Zaroulis, C. G., Posner, J. B., Houde, R. W. & Li, C. H. (1979). γ-endorphin: Analgesic and hormonal effects in humans. Proc. Nat. Acad. Sci. USA, 76, 5377–5381.PubMedCentralPubMedCrossRefGoogle Scholar
  34. Frenk, H., McCarty, B. & Liesbeskind, J. C. (1978). Different brain areas mediate the analgesic and epileptic properties of enkephalin. Science, 200, 335–337.PubMedCrossRefGoogle Scholar
  35. Gillan, M. G. C., Kosterlitz, H. W. & Paterson, S. J. (1980). Comparison of the binding characteristics of tritiated opiates and opioid peptides. Brit. J. Pharmac., in press.Google Scholar
  36. Goldstein, A. & Hilgard, E. R. (1975). Failure of the opiate antagonist naloxone to modify hypnotic analgesia. Proc. Nat. Acad. Sci. USA. 72, 2041–2043.PubMedCentralPubMedCrossRefGoogle Scholar
  37. Graf, L., Kennessy, A., Patthy, A., Grynbaum, A., Marks, N. & Lajtha, A. (1979). Cathepsin D generates γ-endorphin from γ-endorphin. Arch. Biochem. Biophys., 193, 101–109.PubMedCrossRefGoogle Scholar
  38. Grandison, L. & Guidotti, A. (1977). Regulation of prolactin release by endogenous opiates. Nature, 270, 357–359.PubMedCrossRefGoogle Scholar
  39. Grynbaum, A., Kastin, A. J., Coy, D. H. & Marks, N. (1977). Breakdown of enkephalin and endorphin analogs by brain extracts. Brain Res. Bull, 2, 479–484.PubMedCrossRefGoogle Scholar
  40. Guidotti, A. & Grandison, L. (1978). Participation of hypothalamic endorphins in the control of prolactin release. In The Endorphins, Advances in Biochemical Psychopharmacology. Vol. 18. ed., Costa, E. & Trabucchi, M., pp. 191–198. New York: Raven Press.Google Scholar
  41. Guyon, A., Roques, B. P., Guyon, F., Foucault, A., Perdrisot, R., Swerts, J.-P. & Schwartz, J.-C. (1979). Enkephalin degradation in mouse brain studied by a new H.P.L.C. method: further evidence for the involvement of carboxypeptidase. Life Sci., 25, 1605–1612.PubMedCrossRefGoogle Scholar
  42. Hambrook, J. M., Morgan, B. A., Ranee, M. J. & Smith, C. F. C. (1976). Mode of deactivation of the enkephalins by rat and human plasma and rat brain homogenates. Nature, 262, 782–783.PubMedCrossRefGoogle Scholar
  43. Hayes, R. L., Bennett, G. J., Newlon, P. G. & Mayer, D. J. (1978). Behavioral and physiological studies of non-narcotic analgesia in the rat elicited by certain environmental stimuli. Brain Res., 155, 69–90.PubMedCrossRefGoogle Scholar
  44. Henderson, G., Hughes, J. & Kosterlitz, H. W. (1978). In vitro release of leu- and met-enkephalin from the corpus striatum. Nature,271, 677–679.PubMedCrossRefGoogle Scholar
  45. Henriksen, S. J., Bloom, F. E., McCoy, F., Ling, N. & Guillemin, R. (1978). γ-endorphin induces nonconvulsive limbic seizures. Proc. Nat. Acad. Sci. USA, 75, 5221–5225.PubMedCentralPubMedCrossRefGoogle Scholar
  46. Hiller, J. M., Pearson, J. & Simon, E. J. (1973). Distribution of stereo-specific binding of the potent narcotic analgesic etorphine in the human brain: Predominance in the limbic system. Res. Commun, chem. Pathol. Pharmac., 6, 1052–1062.Google Scholar
  47. Hökfelt, T., Ljungdahl, A., Terenius, L., Elade, R. & Nilsson, G. (1977). Immunohistochemical analysis of peptide pathways possibly related to pain and analgesia: Enkephalin and substance P. Proc. Nat. Acad. Sci. USA, 74, 3081–3085.PubMedCentralPubMedCrossRefGoogle Scholar
  48. Holaday, J. W. & Faden, A. I. (1978). Naloxone reversal of endotoxin hypotension suggests role of endorphins in shock. Nature., 275, 450–451.PubMedCrossRefGoogle Scholar
  49. Holaday, J. W. & Faden, A. I. (1980). Naloxone acts at central opiate receptors to reverse hypotension, hypothermia and hypoventilation in spinal shock. Brain Res., 189, 295–299.PubMedCrossRefGoogle Scholar
  50. Höllt, V., Müller, O. A. & Fahlbusch, R. (1979). γ-endorphin in human plasma: basal and pathologically elevated levels. Life Sci, 25, 37–44.PubMedCrossRefGoogle Scholar
  51. Hosobuchi, Y., Rossier, J., Bloom, F. E. & Guillemin, R. (1979). Stimulation of human periaqueductal gray for pain relief increases immunoreactive γ-endorphin in ventricular fluid. Science, 203, 279–281.PubMedCrossRefGoogle Scholar
  52. Hutchinson, M., Kosterlitz, H. W., Leslie, F. M., Waterfield, A. A. & Terenius, L. (1975). Assessment in the guinea-pig ileum and mouse vas deferens of benzomorphans which have strong antinociceptive activity but do not substitute for morphine in the dependent monkey. Brit. J. Pharmac., 55, 541–546.CrossRefGoogle Scholar
  53. Iversen, L. L., Iversen, S. D., Bloom, F. E., Vargo, T. & Guillemin, R. (1978). Release of enkephalin from rat globus pallidus in vitro. Nature, 271, 679–681.PubMedCrossRefGoogle Scholar
  54. Janowsky, D., Judd, L., Huey, L., Roitman, N. & Parker, D. (1979). Naloxone effects on serum growth hormone and prolactin in man. Psychopharmac., 65, 95–97.CrossRefGoogle Scholar
  55. Jessell, T. M. & Iversen, L. L. (1977). Opiate analgesics inhibit substance P release from rat trigeminal nucleus. Nature, 268, 549–551.PubMedCrossRefGoogle Scholar
  56. Kimura, S., Lewis, R. V., Stern, A. S., Rossier, J., Stein, S. & Udenfriend, S. (1980). Probable precursors of [Leu]enkephalin and [Met]enkephalin in adrenal medulla: Peptides of 3–5 kilodaltons. Proc. Nat. Acad. Sci. USA, 77, 1681–1685.PubMedCentralPubMedCrossRefGoogle Scholar
  57. Knight, M. & Klee, W. A. (1978). The relationship between enkephalin degradation and opiate receptor occupancy. J. biol. Chem., 253, 3843–3847.PubMedGoogle Scholar
  58. Kosterlitz, H. W., Lord, J. A. H., Paterson, S. J. & Waterfield, A. A. (1980). Effects of changes in the structure of enkephalins and narcotic analgesic drugs on their interactions with μ-receptors and δ-receptors. Brit. J. Pharmac., 68, 333–342.CrossRefGoogle Scholar
  59. Kosterlitz, H. W. & McKnight, A. T. (1980). Modulatory effects of opioid peptides on neurophysiological functions. In Progress in Sensory Physiology, ed., Ottoson, D. Berlin: Springer, in press.Google Scholar
  60. Kosterlitz, H. W. & McKnight, A. T. (1981). Endorphins and enkephalins. In Advances in Internal Medicine, Vol. 26, ed., Siperstein, M. D. & Stollerman, G. H. Chicago: Year Book Medical Publishers, in press.Google Scholar
  61. Kuhar, M. J., Pert, C. B. & Snyder, S. H. (1973). Regional distribution of opiate receptor binding in monkey and human brain. Nature, 245, 447–450.PubMedCrossRefGoogle Scholar
  62. Lawson, E. E., Waldrop, T. G. & Eldridge, F. C. (1979). Naloxone enhances respiratory output in cats. J. appl. Physiol, 47, 1105–1111.PubMedGoogle Scholar
  63. Lemaire, I., Tseng, R. & Lemaire, S. (1978). Systemic administration of γ-endorphin: Potent hypotensive effect involving a serotonergic pathway. Proc. Nat. Acad. Sci. USA, 75, 6240–6242.PubMedCentralPubMedCrossRefGoogle Scholar
  64. Levine, J. D., Gordon, N. C., Bornstein, J. C. & Fields, H. L. (1979). Role of pain in placebo analgesia. Proc. Nat. Acad. Sci. USA, 76, 3528–3531.PubMedCentralPubMedCrossRefGoogle Scholar
  65. Lewis, R. V., Stein, S., Gerber, L. D., Rubinstein, M. & Udenfriend, S. (1979a). High molecular weight opioid containing proteins in striatum. Proc. Nat. Acad. Sci. USA, 75, 4021–4023.CrossRefGoogle Scholar
  66. Lewis, R. V., Stern, A. S., Rossier, J., Stein, S. & Udenfriend, S. (1979b). Putative enkephalin precursors in bovine and renal medulla. Biochem. Biophys. Res. Commun., 89, 822–829.PubMedCrossRefGoogle Scholar
  67. Lindblom, U. & Tegnér, R. (1979). Are the endorphins active in clinical pain stress? Narcotic antagonism in chronic pain patients. Pain, 7, 65–68.PubMedCrossRefGoogle Scholar
  68. Liotta, A. S., Gildersleeve, D., Brownstein, M. J. & Krieger, D. T. (1979). Biosynthesis in vitro of immunoreactive 31, 000 dalton corticotropin/γ-endorphin-like material by bovine hypothalamus. Proc. Nat. Acad. Sci. USA, 76, 1448–1452.PubMedCentralPubMedCrossRefGoogle Scholar
  69. Lord, J. A. H., Waterfield, A. A., Hughes, J. & Kosterlitz, H. W. (1977). Endogenous opioid peptides: multiple agonists and receptors. Nature, 267, 495–499.PubMedCrossRefGoogle Scholar
  70. Lundberg, J. M., Hökfelt, T., Fahrenkrug, J., Nilsson, G. & Terenius, L. (1979). Peptides in the cat carotid body (glomus caroticum): VIP-, enkephalin-, and substance P-like immuno-reactivity. Acta physiol. Scand., 107, 279–281.PubMedCrossRefGoogle Scholar
  71. McKnight, A. T., Hughes, J. & Kosterlitz, H. W. (1979). Synthesis of enkephalins by guinea-pig striatum in vitro. Proc. Roy. Soc. Lond. B, 205, 199–207.CrossRefGoogle Scholar
  72. McKnight, A. T., Sosa, R. P., Corbett, A. D. & Kosterlitz, H. W. (1980). Enkephalin precursors from guinea-pig myenteric plexus. In Endogenous and Exogenous Opiate Agonists and Antagonists, ed. Way, E. L. pp. 213–216. New York: Pergamon Press.CrossRefGoogle Scholar
  73. McKnight, A. T., Sosa, R. P., Hughes, J. & Kosterlitz, H. W. (1978). Biosynthesis and release of enkephalins. In Characteristics and Function of Opioids. Developments in Neuroscience. Vol. 4. ed. van Ree, J. M. & Terenius, L., pp. 259–269. Amsterdam: Elsevier/North Holland Biomedical Press.Google Scholar
  74. Mains, R. E. & Eipper, B. A. (1978). Coordinate synthesis of corticotropins and endorphins by mouse pituitary tumour cells. J. biol. Chem., 253, 651–655.PubMedGoogle Scholar
  75. Malfroy, B., Swerts, J. P., Guyon, A., Roques, B. P. & Schwartz, J. C. (1978). High-affinity enkephalin-degrading peptidase in brain is increased after morphine. Nature, 276, 523–526.PubMedCrossRefGoogle Scholar
  76. Malfroy, B., Swerts, J.-P., Llorens, C. & Schwartz, J.-C. (1979). Regional distribution of a high affinity enkephalin-degrading peptidase (“enkephalinase”) and effects of lesions suggest localization in the vicinity of opiate receptors in brain. Neurosci. Lett., 11, 329–334.PubMedCrossRefGoogle Scholar
  77. Marks, N., Grynbaum, A. & Neidle, A. (1977). On the degradation of enkephalins and endorphins by rat and mouse brain extracts. Biochem. Biophvs. Res. Commun., 74, 1552–1559.CrossRefGoogle Scholar
  78. Martin, J. B., Tolis, G., Woods, I. & Guyda, H. (1979). Failure of naloxone to influence physiological growth hormone and prolactin secretion. Brain Res., 168, 210–215.PubMedCrossRefGoogle Scholar
  79. Martin, W. R. (1967). Opioid antagonists. Pharmac. Rev., 19, 463–521.Google Scholar
  80. Martin, W. R., Eades, C. G., Thompson, J. A., Huppler, R. E. & Gilbert, P. E. (1976). The effects of morphine- and naloxone-like drugs in the nondependent and morphine-dependent chronic spinal dog. J. Pharmac. exp. Ther., 197, 517–532.Google Scholar
  81. Mayer, D. J. (1979). Endogenous analgesia systems: neural and behavioural mechanisms. In Advances in Pain Research and Therapy. Vol. 3, ed. Bonica, J. J., Liebeskind, J. C. & Albe-Fessard, D. G., pp. 385–410. New York: Raven Press.Google Scholar
  82. Mayer, D. J., Price, D. D. & Rafii, A. (1977). Antagonism of acupuncture analgesia in man by the narcotic antagonist naloxone. Brain Res., 121, 368–372.PubMedCrossRefGoogle Scholar
  83. Meek, J. L., Yang, H.-Y. T. & Costa, E. (1977). Enkephalin catabolism in vitro and in vivo. Neuropharmac., 16, 151–154.CrossRefGoogle Scholar
  84. Mello, N. K. & Mendelson, J. H. (1978). Self-administration of an enkephalin analog by rhesus monkeys. Pharmac. Biochem. Behav., 9, 579–586.CrossRefGoogle Scholar
  85. Mendelson, J. H., Ellingboe, J., Keuhule, J. C. & Mello, N. K. (1979). Effects of naltrexone on mood and neuroendocrine function in normal male adults. Psychoneuroendocrinology, 3, 231–236.CrossRefGoogle Scholar
  86. Nakai, Y., Nakao, K., Oki, S., Imura, H. & Li, C. H. (1978). Presence of immunoreactive γ-endorphin in plasma of patients with Nelson’s syndrome and Addison’s disease. Life Sci, 23, 2293–2298.PubMedCrossRefGoogle Scholar
  87. Nakanishi, S., Inoue, A., Kita, T., Nakamura, M., Chang, A. C. Y., Cohen, S. N. & Numa, S. (1979). Nucleotide sequence of cloned cDNA for bovine corticotropin-γ-lipotropin precursor. Nature, 278, 423–427PubMedCrossRefGoogle Scholar
  88. Osborne, H., Höllt, V. & Herz, A. (1978). Potassium-induced release of enkephalins from rat striatal slices. Eur. J. Pharmac., 48, 219–221.CrossRefGoogle Scholar
  89. Oyama, T., Jin, T., Yamaya, R., Ling, N. & Guillemin, R. (1980). Profound analgesic effects of γ-endorphin in man. Lancet, 1, 122–124.PubMedCrossRefGoogle Scholar
  90. Pert, C. B. & Taylor, D. (1980). Type 1 and Type 2 opiate receptors: a subclassification scheme based upon GTP’s differential effects on binding. In Endogenous and Exogenous Opiate Agonists and Antagonists, ed. Way, E. L. pp. 87–90. New York: Pergamon Press.CrossRefGoogle Scholar
  91. Pezalla, P. D., Seidah, N. G., Benjannet, S., Crine, P., Lis, M. & Chrétien, M. (1978). Biosynthesis of beta-endorphin, beta-lipotropin and the putative ACTH-LPH precursor in the frog pars intermedia. Life Sci, 23, 2281–2292.PubMedCrossRefGoogle Scholar
  92. Rivier, C., Vale, W., Ling, N., Brown, M. & Guillemin, R. (1977). Stimulation in vivo of the secretion of prolactin and growth hormone by γ-endorphin. Endocrinology, 100, 238–240.PubMedCrossRefGoogle Scholar
  93. Roemer, D., Buescher, H. H., Hill, R. C., Pless, J., Bauer, W., Cardinaux, F., Closse, A., Hauser, D. & Huguenin, R. (1977). A synthetic enkephalin analogue with prolonged parenteral and oral analgesic activity. Nature, 268, 547–549.PubMedCrossRefGoogle Scholar
  94. Rossier, J., Lewis, R. V., Stern, A. S., Stein, S. & Udenfriend, S. (1979). Bovine adrenals contain high levels of enkephalins and even higher levels of several putative enkephalin precursors. Abs. Soc. Neuroscience, 5, 538.Google Scholar
  95. Schultzberg, M., Hökfelt, T., Lundberg, J. M., Terenius, L., Elfvin, L.-G. & Elde, R. (1978). Enkephalin-like immunoreactivity in nerve terminals in sympathetic ganglia and adrenal medulla and in adrenal medullary gland cells. Acta physiol. Scand., 103, 475–477.PubMedCrossRefGoogle Scholar
  96. Shaar, C. J., Frederickson, R. C. A., Dininger, N. B. & Jackson, L. (1977). Enkephalin analogues and naloxone modulate the release of growth hormone and prolactin — evidence forregulation by an endogenous opioid peptide in brain. Life Sci, 21, 853–860.PubMedCrossRefGoogle Scholar
  97. Sjölund, B., Terenius, L. & Eriksson, M. (1977). Increased cerebrospinal fluid levels of ndorphins after electroacupuncture. Acta physiol. Scand., 100, 382–384.PubMedCrossRefGoogle Scholar
  98. Smith, T. W., Hughes, J., Kosterlitz, H. W. & Sosa, R. P. (1976). Enkephalins: isolation, istribution and function. In Opiates and Endogenous Opioid Peptides, ed. Kosterlitz, H. W. pp. 57–62. Amsterdam: Elsevier/North Holland Biomedical Press.Google Scholar
  99. Sosa, R. P., McKnight, A. T., Hughes, J. & Kosterlitz, H. W. (1977). Incorporation of labelled amino acids into the enkephalins. FEBS Lett., 84, 195–198.PubMedCrossRefGoogle Scholar
  100. Stacher, G., Bauer, P., Steinringer, H., Schreiber, E. & Schmierer, G. (1979). Effects of the synthetic enkephalin analogue FK 33–824 on pain threshold and pain tolerance in man. Pain, 7, 159–172.PubMedCrossRefGoogle Scholar
  101. Stein, L. & Belluzzi, J. D. (1979). Brain endorphins: possible mediators of pleasurable states. In Endorphins in Mental Health Research, ed. Usdin, E., Bunney, W. E. & Kline, N. S. pp. 375–389. London: Macmillan Press.CrossRefGoogle Scholar
  102. Suda, T., Liotta, A. S. & Krieger, D. T. (1978). γ-endorphin is not detectable in plasma from normal human subjects. Science, 202, 221–223.PubMedCrossRefGoogle Scholar
  103. Sullivan, S., Akil, H. & Barchas, J. C. (1979). In vitro degradation of enkephalin: evidence for cleavage of the Gly-Phe bond. Commun. Psychopharmac., 2, 525–531.Google Scholar
  104. Székely, J. I., Rónai, A. Z., Dunai-Kovács, Z., Miglécz, E., Berzétei, I., Bajusz, S. & Gráf, L. (1977). (D-Met2, Pro5)-Enkephalinamide: a potent morphine-like analgesic. Eur. J. Pharmac., 43, 293–294.CrossRefGoogle Scholar
  105. Urca, G., Frenk, H., Liebeskind, J. C. & Taylor, A. N. (1977). Morphine and enkephalin: analgesic and epileptic properties. Science, 197, 83–86.PubMedCrossRefGoogle Scholar
  106. Viveros, O. H., Diliberto, E. J., Hazum, E. & Chang, K.-J. (1979). Met- and leu-enkephalins and met-enkephalin-like peptides in the adrenal medulla: studies on storage, secretion and synthesis. Abs. Soc. Neuroscience, 5, 543.Google Scholar
  107. Vogel, Z. & Alstein, M. (1977). The adsorption of enkephalin to porous polystyrene beads: a simple assay for enkephalin hydrolysis. FEBS Lett, 80, 332–336.PubMedCrossRefGoogle Scholar
  108. von Knorring, L., Almay, B. G. L., Johansson, F. & Terenius, L. (1978). Pain perception and endorphin levels in cerebrospinal fluid. Pain, 5, 359–365.CrossRefGoogle Scholar
  109. Walker, J. M., Sandman, C. A., Berntson, G. G., McGivern, R. F., Coy, D. H. & Kastin, A. J. (1977). Endorphin analogs with potent and long-lasting analgesic effects. Pharmac. Biochem. Behav., 7, 543–548.CrossRefGoogle Scholar
  110. Watson, S. J., Akil, H., Berger, P. A. & Barchas, J. D. (1979). Some observations on the opiate peptides and schizophrenia. J. gen. Psychiat., 36, 35–41.CrossRefGoogle Scholar
  111. Yang, H.-Y. T., Costa, E., Di Giulio, A. M., Fratta, W. & Hong, J. S. (1979). Met-enkephalin (ME)-like peptides in bovine adrenal gland: characterization of possible ME precursors. Fed. Proc., 38, Abs. 711.Google Scholar

Copyright information

© The contributors 1980

Authors and Affiliations

  • H. W. Kosterlitz
    • 1
  1. 1.Unit for Research on Addictive DrugsUniversity of AberdeenAberdeenScotland, UK

Personalised recommendations