Control Mechanisms in the Enzyme Hydrolysis of Adrenal-Released Enkephalins

  • L. Giorgio Roda
  • Gianna Roscetti
  • Roberta Possenti
  • Francesca Venturelli
  • Fabrizio Vita


Opioid peptides are secreted by the adrenal medulla where they are stored within the chromaffin granule (1-3). Consequently, these peptides are released into the blood stream together with the whole soluble content of the granule during the. physiological activity of the gland.


Enzyme Hydrolysis Human Plasma Adrenal Medulla Incubation Mixture 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. 1.
    Terenius, L. and Wahlstrom, A. (1974) Inhibitor(s) of narcotic receptor binding in brain extracts and cerebrospinal fluid. Acta Pharmacol. Toxicol. (suppl. 1 ) 35, 55.Google Scholar
  2. 2.
    Hughes, J. (1975) Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine. Brain Research 88, 295–308.Google Scholar
  3. 3.
    Pasternak, K.W., Goodman, R. and Snyder S.H. (1975) An endogenous morphine-like factor in mammalian brain. Life Sci. 16, 1765–1769.PubMedCrossRefGoogle Scholar
  4. 4.
    Pert, C.B., Pert, A., Chang, J.K. and Fond, B.T.W. (1976) D-Ala2-MetEnkephalinide: a potent, long-lasting synthetic pentapeptide analgesic. Science 194, 330–32.Google Scholar
  5. 5.
    Buscher, H.H., Hill, R.C., Romer, D., Cardinaux, F., Closse, A., Hauser, D. and Pless, J. (1976) Evidence for analgesic activity of enkephalin in the mouse. Nature 261, 423–25.Google Scholar
  6. 6.
    Belluzzi, J.D., Grant, N., Garsky, V., Sarantakis, D., Wise, C.D., and Stein, L. (1976) Analgesia indiced in vivo by central administration of enkephalin in rat. Nature 260, 625–26.Google Scholar
  7. 7.
    Terenius, L., (1978) Endogenous peptides and analgesia. Ann. Rev. Pharmacol. Toxicol. 18, 189–204.CrossRefGoogle Scholar
  8. 8.
    Hambrook, J.M., Morgan, B.A., Rance, M.J., and Smith, C.F.C., (1976) Mode of deactivation of the enkephalins by rat and human plasma and rat brain homogenates. Nature 262, 782–783.Google Scholar
  9. 9.
    Dupont, A., Cusan, L., Garon, M., Alvarado-Urbina, G. and Labrie, F. (1977) Extremely rapid degradation of 3H methionine-enkephalin by various rat tissues in vivo and in vitro. Life Sci. 21, 907–914.Google Scholar
  10. 10.
    Hogue-Angeletti, R.A. and Roda, L.G. (1980) In vitro interaction of enkephalin with serum and chromaffin granule components. Experientia 36, 1420–1421.Google Scholar
  11. 11.
    Schwartz, J.C., Malfroy, B. and De La Baume, S. (1981) Biological inactivation of enkephalins and the role of enkephalin-dipeptidylcarboxypeptidase (“Enkephalinase”) as neuropeptidase. Life Sci. 29, 1715–1740.PubMedCrossRefGoogle Scholar
  12. 12.
    Coletti-Previero, M.A., Matras, H., Descomps. B. and Previero, A. (1981) Purification and substrate characterization of a human enkephalin-degrading aminopeptidase. Biochem. Biophys. Acta 657, 122–127.Google Scholar
  13. 13.
    Roscetti, G., Possenti, R., Bassano, E. and Roda, L.G. (1984) Mechanisms of leu-enkephalin hydrolysis in human blood. Life Sci. in press.Google Scholar
  14. 14.
    Roda, L.G., De Marco, V. and Possenti, R. (1983) Stability of periphral enkephalins in “Degradation of Endogenous Opioid.” S. Ehrenpreis and F. Sicuteri eds. pgs. 25–42 Raven Press, New York.Google Scholar
  15. 15.
    Loew, G.H. and Burt, S.K. (1978) Energy conformation study of met-enkephalin and its D-Ala2 analogue and their resemblance to ridig opiates. Proc. Natl. Acad. Sci. USA 75, 7–11.Google Scholar
  16. 16.
    Momany, F.A. (1977) Conformational analysis of methionine-enkephalin and some analogs. Biochem. Biophys. Res. Comm. 75, 1098–1103.Google Scholar
  17. Isogai, Y., Nemethy, G. and Scherga, H.A.(1977) Enkephalin-conformational analysis by means of empirical energy calculations. Proc. Natl. Acad. Sci. USA 74,414–418.Google Scholar
  18. 18.
    Spirites, M.A.,Schwartz, R.W., Mattice, W.L. and Coy,D.H. (1978) Circular dichroism and adsorption study of the structure of methionine-enkephalin in solution. Biochem. Biophys. Res. Comm. 81, 602–609.Google Scholar
  19. 19.
    Khaled,M.A., Long, M.M., Thompson, W.D., Bradley, R.J., Brown, G.B., and Urry, D.W. (1977) Conformational states of enkephalin in solution. Biochem. Biophys. Res. Comm. 76, 224–231.Google Scholar
  20. 20.
    Fillippi, B. Gusti, P., Cima, L. Borin, G., Ricchielli, F. and Marchiori f. (1979) Synthetic enkephalins. Intl. J. Peptide Protein Res. 14, 34–40.CrossRefGoogle Scholar
  21. Levine, B.A.,Rabenstein, D.L., Smith, D. and Williams, R.J.P.(1979) Proton magnetic resonance studies on methionine enkephalin and 8-endorphin in aqueous solution. Biochem. Biophys. Acta 579, 279–291.Google Scholar
  22. 22.
    Garbay-Jaureguiberry, C,, Marion, D., Fellion, E. and Roques, B.P. (1982) Refinement of conformational preferences of Leu-enkephalin and Tyr-GlyGly-Phe by 15N NMR. Int. J. Peptide Protein Res. 20, 443–450.CrossRefGoogle Scholar
  23. 23.
    Jones,C.R., Garsky, V. and Gibbons, W.A. (1977) Molecular conformations of met-enkephalin: comparition of the zwitterionic and cationic forms. Biochem. Biophys. Res. Comm. 76, 619–625.Google Scholar
  24. 24.
    Garbay-Jaureguberry, C.,Roques, B.P. and Oberlin,R. (1977) 1H and 13C NMR studies of conformational behavior of leu-enkephalin. FEBS Letters 76,93–98.Google Scholar
  25. 25.
    Smith, G.D. and Griffin, J.F. (1978) Conformation of Leu5 enkephalin from x-ray diffraction: features important for recognition at opiate receptor. Science 199, 1214–1216Google Scholar
  26. 26.
    Cabassi, F. and Zetta, L. (1982) Human 8-endorphin. Intl. J. Peptide Protein Res. 20, 154–158.CrossRefGoogle Scholar
  27. 27.
    Clement-Jones,V., Lovry, P.J.,Rees, L.H. and Besser,G.M. (1980) Conformation of Leu5 enkephalin from x-ray diffraction: features important for recognition at opiate receptor. Nature 283, 295–297.Google Scholar
  28. 28.
    Ryder, S.W. and Eng, J. (1982) Radioimmunoassay of leucine-enkephalin like substance in human and canine plasma. J. Clin. Endocrinol. and Metabolism 52, 367–369.CrossRefGoogle Scholar
  29. Blaschko, H. and Welch, A.D.(1953) Localization of adrenaline in cytoplasmic particles of the bovine adrenal medulla. Naunyn Schmiedberg’s Arch. Exp. Pathol. Pharmakol. 219, 17–22.Google Scholar
  30. Hillarp, N.A., Lagenstedt, S. and Nilson, B. (1953) The isolation of a granular fraction from the suprarenal medulla, containing the sympathomimetic catechol amines. Acta. Phisiol. Scand. 29, 251–263.Google Scholar
  31. 31.
    Winkler, H. (1976) The conposition of adrenal chromaffin granules: an assessment of controversial results. Neuroscience 1, 65–80.Google Scholar
  32. Njus, D. and Radda, G.K. (1978). Bioenergetic processes in chromaffin granules: a new prospective on some old problems. Biochem. Biophys. Acta. 463, 219–244.Google Scholar
  33. 33.
    Hogue-Angeletti, R.A., Roda, L.G., Nolan, J.A. and Zarenba, S. Catecholamine storage vesicles in “Protein of the Nervous System” R.A. Bradshaw and D.M. Schneider eds. Raven Press. New York 1980.Google Scholar
  34. 34.
    Schultzberg, M., Lundberg, J.M., Hokfelt, J., Terenius, L., Brandt, J., Elde, R.P. and Goldstein, M. (1978) Enkephalin-like immunoreactivity in gland cells and nerve terminals of the adrenal medulla. Neuroscience 3, 1169–1186.Google Scholar
  35. Viveros, 0.H., Diliberto, E.J.J., Hazum, E. and Chang, K.J. (1979) Opiate-like materials in the adrenal medulla: evidence for storage and secretion with catecholamines. Mol. Pharmacol. 16, 1101–1108.Google Scholar
  36. 36.
    Di Giulio, A.M., Yang, H.-Y.T., Fratta, W. and Costa, E. (1979). Decreased content of immunoreactive enkephalin-like peptide in peripheral tissues of spontaneously hypertensive rats. Nature 278 646–647.Google Scholar
  37. Lewis, R.V., Stern, A.S., Rossier, J., Stein, S. and Udenfriend, S. (1979) Putative enkephalin precursor in bovine adrenal medulla. Biochem Biophys. Res. Comm. 89, 822–829.Google Scholar
  38. Stern, A.S., Lewis, R.V., Kimura, S., Rossier, J., Stein, S. and Udenfriend, S. (1979) Isolation of the opioid heptapeptide metenkephalin-Arg6-Phe7 from bovine adrenal medullary granules and striatum. Proc. Natl. Acad. Sci. USA 76, 6680–6683.Google Scholar
  39. 39.
    Lewis, R.V., Stern, A.S., Kimura, S., Rossier, J., Brink, L., Gerber, L.D., Stein, S. and Udenfriend, S. Opioid peptides and precursor in the adrenal medulla in “Neural Peptides and Neural Communication.” E. Costa and M. Trabucchi eds. Raven Press, New York 1980.Google Scholar
  40. 40.
    Yang, H.-Y.T., Di Giulio, A.M., Fratta, W., Hong, J.S., Majane, E.A. and Costa, E. (1980) Enkephalin in bovine adrenal gland: multiple molecular forms of Met5-enkephalin immunoreactive peptides. Neuropharmacology 19, 209–215.PubMedCrossRefGoogle Scholar
  41. 41.
    Troy, C.M. and Musacchio, J.M. (1982) Processing of enkephalin precursors by chromaffin granule enzymes. Life Sci. 31, 1717–1720.PubMedCrossRefGoogle Scholar
  42. Wallace, E.F., Evans, C.J., Jurik, S.M., Mafford, I.N. and Barchas, J.D. (1982) Carboxypeptidase B activity from adrenal medulla. Is it involved in the processing of proenkephalin? Life Sci. 31, 1793–1796.Google Scholar
  43. Jones B.N., Shively J.E., Kilpatrick D.L., Stern A.S., Lewis R.V., Kojima K., Udenfriend S., Usa (1979) Adrenal opioid proteins of 8,600 and 12,600 daltons: intermediates in proenkephalin processing. Proc. Natl. Acad. Sci. 2096–2100.Google Scholar
  44. 44.
    Lewis, R.V., Stern, A.S., Kimura, S., Rossier, J., Stein, S. and Udenfriend, S., (1980). An about 50,000-dalton protein in adrenal medulla: a common precursor of Met-and Leu-enkephalin. Science 208, 1459–1461.Google Scholar
  45. 45.
    Fricker, L.D., Supattapone, S. and Snyder, S. (1982) Enkephalin convertase: a specific enkephalin synthesizing carboxypeptidase in adrenal chromaffin granules, brain, and pituitary gland. Life Sci. 31, 1841–1844.Google Scholar
  46. 46.
    Lindberg, I., Yang, H.-Y.T. and Costa, E. (1982) Characterization of a partially pufified trypsin-like enkephalin-generating enzyme in bovine adrenal medulla. Life Sci. 31, 1713–1716.PubMedCrossRefGoogle Scholar
  47. Lewis, R.V. and Stern, A.S. (1983) Biosynthesis of enkephalins and enkephalin-containing polypeptides. Ann. Rev. Pharmacol. Toxicol. 23, 353–372.Google Scholar
  48. Possenti, R., De Marco, V., Cherubini, 0. and Roda, L.G. (1983) Enkephalin-binding systems in human plasma. Neurochem. Res. 8, 423–432.Google Scholar
  49. Hogue-Angeletti, R.A. and Sheetz, PxB. (1978) A soluble lipid protein complex from bovine adrenal medulla chromaffin granules. J. Biol. Chem. 253, 5613–5616.Google Scholar
  50. Helle, K.B. (1966) Antibody formation against soluble protein from bovine adrenal medulla chromaffin granules. Biochem, Biophys. Acta 117, 107–110.Google Scholar
  51. 51.
    Roda, L.G. and Hogue-Angeletti, R.A. (1979) Peptides in the adrenal medulla chromaffin granule. FEBS Letters 107, 393–397.PubMedCrossRefGoogle Scholar
  52. 52.
    Stefano, G.B. and Catapane, E.J. (1979) Enkephalins increase dopamine levels in the CNS of a marine mollusc. Life Sci. 24, 1617–1622.Google Scholar
  53. 53.
    Sundler, F., Hakanson, R., Alumets, J. and Walles, B. (1977) Neuronal localization of pancreatic polypeptide (PP) and vasoactive intestinal peptide (VIP) immunoreactivity in the earthworm (lubricus terrestris). Brain Research Bull. 2, 61–65.Google Scholar
  54. 54.
    Zipser, B. (1980) Identification of specific leech neurones immunoreactive to enkephalin. Nature 283, 857–858.Google Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • L. Giorgio Roda
    • 1
  • Gianna Roscetti
    • 2
  • Roberta Possenti
    • 2
  • Francesca Venturelli
    • 2
  • Fabrizio Vita
    • 2
  1. 1.Laboratorio di FarmacologiaUniversity of AnconaAnconaItaly
  2. 2.Cattedra di Fisiologia Umana“Tor Vergata” UniversityRomeItaly

Personalised recommendations