Enkephalin Release from the Globus Pallidus: In Vitro and in Vivo Studies

  • A. Bayón
  • R. Drucker-Colín
  • L. Lugo
  • W. J. Shoemaker
  • R. Azad
  • F. E. Bloom


The presence of the opioid peptides [5-methionine] -enkephalin (Met-enkephalin) and [5-leucine] -enkephalin (Leu-enkephalin) (7) in several regions of the central nervous system (17) and the immunohistochemical evidence for their location in fibers and cell bodies (6) first supported their consideration as putative central neurotransmitters. The search for a model system to study the central neurobiology of the enkephalins has led to the striatum and especially the globus pallidus because this region has the highest content of immuno-reactive enkephalin and enkephalin-containing fibers. The early studies in one of our laboratories (8) showed that during in vitro perfusion of slices from rat globus pallidus, enkephalin-like immuno-reactive material was released by 50 mM K+ in a Cat2+dependent manner. In subsequent work (1) we have analyzed the composition of these enkephalin-like substances, both in fresh and perfused tissue and in the released material, and also some aspects of the metabolic changes of enkephalins during in vitro release experiments. Based on these studies, we have explored the basic characteristics of enkephalin release from pallidal tissue in unanesthetized-freely moving animals using a push-pull cannula perfusion technique. Our results show that enkephalins can be released from the pallidum, not only by chemical stimulation of the local fibers but also, in a more physiological manner, by electrical stimulation of the caudate nucleus.


Caudate Nucleus High Pressure Liquid Chromatography Globus Pallidus Perfuse Medium Minimum Detectable Amount 
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  1. 1.
    Bayón, A., Koda, L., Battenberg, E., Azad, R., Guillemin, R., and Bloom, F.E., Regional distribution of endorphin, methionine-enkephalin and leucine-enkephalin in the pigeon brain, Neurosei. Letters, 16 (1980) 75–80.Google Scholar
  2. 2.
    Bayón, A., Rossier, J., Mauss, A., Bloom, F.E., Iversen, L.L., Ling, N. and Guillemin, R., In vitro release of methionines-enkephalin and leucine5-enkephalin from the rat globus pallidus, Proc. Natl. Acad. Sei. U.S.A., 75 (1978) 3503–3506.CrossRefGoogle Scholar
  3. 3.
    Cuello, A.C. and Paxinos, G., Evidence for a long Leu-enkephalin strio-pallidal pathway in rat brain, Nature 271 (1978) 178–180.PubMedCrossRefGoogle Scholar
  4. 4.
    Gros, C., Pradelles, P., Rougeot, C., Bepoldin, O., Dray, F., Fournie-Zaluski, M.C., Roques, B.P., Pollard H., Llorens-Cortes, C. and Schwartz, J.C., Radioimmunoassay of methionine-and leucine-enkephalins in regions of rat brain and comparison with endorphins estimated by a radio receptor assay, J. Neurochem., 31 (1978) 29–39.PubMedCrossRefGoogle Scholar
  5. 5.
    Henderson, G., Hughes, J. and Kosterlitz, H.W., In vitro release of Leu-and Met-enkephalin from Corpus striatum. Nature 271 (1978) 677–679.PubMedCrossRefGoogle Scholar
  6. 6.
    Hokfelt, T., Eide, R., Johansson, 0., Terenius, L. and Stein, L., The distribution of enkephalin immunoreactive cell bodies in the rat central nervous system, Neurosci. Letters, 5 (1977) 25–31.Google Scholar
  7. 7.
    Hughes, J., Smith, T.W., Kosterlitz, H.W., Fothergill, L.H. Morgan, B.A. and Morris, H., Identification of two related pentapeptides from the brain with potent opiate agonist activity, Nature, 255 (1975) 577–579.CrossRefGoogle Scholar
  8. 8.
    Iversen, L.L., Iversen, S.D., Bloom, F.E., Vargo, T. and Guillemin, R., Release of enkephalin from rat globus pallidus in vitro, Nature 271 (1978) 679–681.PubMedCrossRefGoogle Scholar
  9. 9.
    Iversen, L.L., Iversen S.D., Bloom, F., Douglas, C., Brown, M. and Vale, W., Calcium-dependent release of somatostatin and neurotensin from rat brain in vitro, Nature, 273 (1978) 161–163.PubMedCrossRefGoogle Scholar
  10. 10.
    Konig, J.F.R. and Klippel, R.A., The Rat Brain, Krieger, Huntington, New York, 1967.Google Scholar
  11. 11.
    Ling, N., Solid phase synthesis of porcine a-endorphin and y-endorphin, two hypothalamic-pituitary peptides with opiate activity, Biochem. Biophys. Res. Commun., 74 (1977) 248–255.CrossRefGoogle Scholar
  12. 12.
    Myers, R.D., An improved push-pull cannula system for perfusing an isolated region of the brain, Physiol. Behavior, 5 (1970) 243–246.Google Scholar
  13. 13.
    Rossier, J., Bayón, A., Vargo, T.M., Ling, N., Guillemin, R. and Bloom, F.E., Radioimmunoassay of brain peptides. Evaluation of a methodology for the assay of B-endorphin and enkephalin, Life Sci., 21 (1977) 847–852.PubMedCrossRefGoogle Scholar
  14. 14.
    Rossier, J., Vargo, T.M., Minick, S., Ling, N., Bloom, F. and Guillemin, R., Regional dissociation of -endorphin and enkephalin contents in rat brain and pituitary, Proc. Natl. Acad. Sci. USA, 74 (1977) 5162–5165.PubMedCrossRefGoogle Scholar
  15. 15.
    Sar, M., Stumpf, W.E., Miller, R.J., Chang, K.-J. and Cuatrecasas, P., Immunohistochemical localization of enkephalin in rat brain and spinal cord, J. Comp. Neurol. 182 (1978) 17–38.PubMedCrossRefGoogle Scholar
  16. 16.
    Stern, A.S., Lewis, R.V., Kimura, S., Rossier, J., Gerber, L.D., Brink, L., Stein, S. and Udenfriend, S., Isolation of the opioid heptapeptide Met-enkephalin-Arg6-Phe7 from bovine adrenal medullary granules and striatum, Proc. Natl. Acad. Sci. USA 76 (1979) 6680–6683.PubMedCrossRefGoogle Scholar
  17. 17.
    Yang, H.-Y., Hong, J.S. and Costa, EM Regional distribution of Leu-and Met-enkephalin in rat brain, Neuropharmacology, 16 (1977) 303–307.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • A. Bayón
    • 1
  • R. Drucker-Colín
    • 1
  • L. Lugo
    • 1
  • W. J. Shoemaker
    • 2
  • R. Azad
    • 2
  • F. E. Bloom
    • 2
  1. 1.Departamento de Neurociencias, Centro de Investigaciones en Fisiología CelularUniversidad Nacional Autónoma de MéxicoMéxico 20, D.FMexico
  2. 2.Arthur V. Davis Center for Behavioral NeurobiologyThe Salk InstituteLa JollaUSA

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