Effects of Acidic Dipeptides on Aminoacidergic Neurotransmission in the Brain

  • V. Varga
  • Kirsi-Marja Marnela
  • Pirjo Kontro
  • J. Gulyás
  • Z. Vadász
  • P. Lähdesmäki
  • S. S. Oja
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 217)

Abstract

Among the numerous oligopeptides found in the brain the small acidic peptides have received little attention, although their existence has long been known (5, 6, 36, 38). These substances are often acetylated and contain aspartate, glutamate, serine, glycine, alanine and taurine in various combinations (9, 30, 37, 40). Of the taurine-containing peptides the most plentiful and best known is L-glutamyl-taurine (31), which exists in two forms, alpha and gamma, in approximately equal amounts in calf brain synaptic vesicles (32). Their origin is still obscure, although the biosynthesis of γ-glutamyl-taurine has been shown to be catalyzed by γ-glutamyl-transferase (42). Various effects have been attributed to γ-glutamyl-taurine in different organisms (10). However, the physiological role of all the above mentioned peptides has so far remained entirely unknown in the case of the brain. We have therefore studied the effects of glutamyl-taurine and some synthetic analogs on the actions of putative neurotransmitter amino acids.

Keywords

Glutamate Release Gaba Release Amino Acid Uptake Synaptic Membrane Excitatory Amino Acid 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.

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References

  1. 1.
    Arbilla, S., Kamal, L., and Langer, S.Z., 1979, Presynaptic GABA autoreceptors on GABAergic nerve endings of the rat substantia nigra, Eur. J. Pharmac, 57: 211–217.CrossRefGoogle Scholar
  2. 2.
    Baudry, M., Siman, R., Smith, E.W., and Lynch, G., 1983, Regulation by calcium ions of glutamate receptor binding in hippocampal slices, Eur. J. Pharmac, 90: 161–166.CrossRefGoogle Scholar
  3. 3.
    Braestrup, C., Nielsen, M., Krogsgaard-Larsen, P., and Falch, E., 1979, Partial agonists for brain GABA/benzodiazepine receptor complex, Nature, 280: 331–333.PubMedCrossRefGoogle Scholar
  4. 4.
    Chesselet, M.-F., 1984, Presynaptic regulation of neurotransmitter release in the brain: facts and hypothesis, Neuroscience, 12: 347–375.PubMedCrossRefGoogle Scholar
  5. 5.
    Cheung, S.T., and Lim, R., 1979, Isolation of γ-glutamylasPartic acid and α-aspartylalanine from pig brain, Biochim. Blophys. Acta, 586: 418–424.CrossRefGoogle Scholar
  6. 6.
    Curatolo, A., d’Arcangelo, P., Lino, A., and Brancati, A., 1965, Distribution of N-acetyl-aspartic and N-acetyl-aspartyl-glutamic acids in nervous tissue, J. Neurochem., 12: 339–342.PubMedCrossRefGoogle Scholar
  7. 7.
    Davis, J., and Watkins, J.C., 1981, Differentiation of kainate and quisqualate receptors in the cat spinal cord by selective antagonism with γ-D-(and L-)glutamylglycine, Brain Res., 206: 172–177.CrossRefGoogle Scholar
  8. 8.
    Fagg, G.E., 1985, L-Glutamate, excitatory amino acid receptors and brain function, Trends Neuroscl., 8: 207–210.CrossRefGoogle Scholar
  9. 9.
    Feuer, L., 1977, Theoretical background of the recognition of a new bioactive substance, Litoralon, isolated from the parathyroid. Further theoretical considerations, Biologia (Budapest), 25: 3–33.Google Scholar
  10. 10.
    Feuer, L., 1981, Biological effects of gamma-L-glutamyl taurine (glutaurine): A new parathyroid hormone, in: “The Effects of Taurine on Excitable Tissues”, S.W. Schaffer, S.I. Baskin and J.J. Kocsis, eds., Spectrum Publications, New York, pp. 31–39.CrossRefGoogle Scholar
  11. 11.
    Foster, A.A., and Fagg, G.E., 1984, Acidic amino acid binding sites in mammalian neuronal membranes: their characteristics and relationship to synaptic receptors, Brain Res. Rev., 7: 103–163.CrossRefGoogle Scholar
  12. 12.
    Hajos, F., 1975, An improved method for the preparation of synaptosomal fraction in high purity, Brain Res., 93: 485–489.PubMedCrossRefGoogle Scholar
  13. 13.
    Hall, J.G., Hicks, T.P., and McLennan, H., 1978, Kainic acid and the glutamate receptor, Neurosci. Lett., 8: 171–175.CrossRefGoogle Scholar
  14. 14.
    Jones, A.W., Smith, D.A.S., and Watkins, J.C., 1984, Structure-activity relations of dipeptide antagonists of excitatory amino acids, Neuroscience, 13: 573–581.PubMedCrossRefGoogle Scholar
  15. 15.
    Kanazawa, A., Kakimoto, Y., Nakajima, T., Sano, I., Shimizu, H., and Takesada, M., 1965, Isolation and identification of γ-L-glutamylglycine from bovine brain, Biochlm. Biophys. Acta, 97: 460–464.CrossRefGoogle Scholar
  16. 16.
    Karobath, M., and Sperk, G., 1979, Stimulation of benzodiazepine receptor binding by γ-aminobutyric acid, Proc. Natl Acad. Sci. USA, 76: 1004–1006.PubMedCrossRefGoogle Scholar
  17. 17.
    Koller, K.J., and Coyle, J.T., 1985, The characterization of the specific binding of [3H]-N-acetylaspartylglutamate to rat brain membranes, J. Neurosci., 5: 2882–2888.PubMedGoogle Scholar
  18. 18.
    Kontro, P., 1984, Comparison of taurine, hypotaurine and β-alanine uptake in brain synaptosomal preparations from developing and adult mouse, Int. J. Dev. Neurosci., 2: 465–470.CrossRefGoogle Scholar
  19. 19.
    Kontro, P., and Oja, S.S., 1978, Taurine uptake by rat brain synaptosomes, J. Neurochem., 30: 1297–1304.PubMedCrossRefGoogle Scholar
  20. 20.
    Kontro, P., and Oja, S.S., 1984, Binding and uptake of taurine and GABA in developing and adult mouse brain, Acta Univ. Tamper. [B], 21: 60–67.Google Scholar
  21. 21.
    Kontro, P., and Oja, S.S., 1987, Effects of the anticonvulsive taurine derivative, taltrimide, on membrane transport and binding of GABA and taurine in the mouse brain, Neuropharmacology, 26: 19–23.PubMedCrossRefGoogle Scholar
  22. 22.
    Kontro, P., and Oja, S.S., 1987, Taurine and GABA release from mouse cerebral cortex slices: effects of structural analogues and drugs, Neurochem. Res., 12: 475–482.PubMedCrossRefGoogle Scholar
  23. 23.
    Korpi, E.R., and Oja, S.S., 1979, Efflux of phenylalanine from rat cerebral cortex slices as influenced by extra-and intracellular amino acids, J. Neurochem., 32: 789–796.PubMedCrossRefGoogle Scholar
  24. 24.
    Korpi, E.R., and Oja, S.S., 1984, Comparison of two superfusion systems for study of neurotransmitter release from rat cerebral cortex slices, J. Neurochem., 43: 236–242.PubMedCrossRefGoogle Scholar
  25. 25.
    Krogsgaard-Larsen, P., Hjeds, H., Curtis, D.R., Lodge, D., and Johnston, G.A.R., 1979, Dihydromuscimol, thiomuscimol and related heterocyclic compounds as GABA analogues, J. Neurochem., 32: 1717–1724.PubMedCrossRefGoogle Scholar
  26. 26.
    Lähdesmäki,’ P., and Oja, S.S., 1973, On the mechanism of taurine transport at brain cell membranes, J. Neurochem., 20: 1411–1417.PubMedCrossRefGoogle Scholar
  27. 27.
    Larder, A.P., and McLennan, H., 1983, Binding sites for L-glutamate in the central nervous system of the rat, Neurochem. Res., 9: 393–403.CrossRefGoogle Scholar
  28. 28.
    London, E., and Coyle, J.T., 1978, Specific binding of [3H]kainic acid to receptor sites in rat brain, Mol. Pharmac., 15: 492–505.Google Scholar
  29. 29.
    Malminen, O., and Kontro, P., 1986, Modulation of the GABA-benzo-diazepine receptor complex by taurine in rat brain membranes, Neurochem. Res., 11: 85–94.PubMedCrossRefGoogle Scholar
  30. 30.
    Marnela, K.-M., Timonen, M., and Lähdesmäki, P., 1984, Mass spectrometric analyses of brain synaptic peptides containing taurine, J. Neurochem., 43: 1650–1653.PubMedCrossRefGoogle Scholar
  31. 31.
    Marnela, K.-M., Morris, H.R., Panico, M., Timonen, M., and Lähdesmäki; P., 1985, Glutamyl-taurine is the predominant synaptic taurine peptide, J. Neurochenu, 44: 752–754.CrossRefGoogle Scholar
  32. 32.
    Marnela, K.-M., Varga, V., Dibó, G., and Lähdesmäki, P., 1987, Position of the peptide linkage in glutamyl-taurine from calf brain synaptic vesicles, J. Neurochem., 48, in press.Google Scholar
  33. 33.
    McBean, G.J., and Roberts, P.J., 1981, Glutamate-preferring receptors regulate the release of D-[3H]aspartate from rat hippocampal slices, Nature, 291: 593–594.PubMedCrossRefGoogle Scholar
  34. 34.
    Meyerhoff, J.L., Koller, K.J., Walczak, D.D., and Coyle, J.T., 1985, Regional brain levels of N-acetyl-aspartyl-glutamate: the effect of kindled seizures, Brain Res., 346: 392–396.PubMedCrossRefGoogle Scholar
  35. 35.
    Oja, S.S., and Korpi, E.R., 1983, Amino acid transport, in: “Handbook of Neurochemistry, 2nd edn, Vol 5”, A. Lajtha, ed., Plenum Press, New York, pp. 311–337.Google Scholar
  36. 36.
    Reichelt, K.L., and Fonnum, F., 1969, Subcellular localization of N-acetyl-aspartyl-glutamate, N-acetylglutamate and glutathione in brain, J. Neurochem., 16: 1409–1416.PubMedCrossRefGoogle Scholar
  37. 37.
    Reichelt, K.L., and Kvamme, E., 1973, Histamine-dependent formation of N-acetyl-aspartyl peptides in mouse brain, J. Neurochem., 21: 849–859.PubMedCrossRefGoogle Scholar
  38. 38.
    Sano, I., 1970, Simple peptides in brain, Int. Rev. Neurobiol., 12: 235–263.PubMedCrossRefGoogle Scholar
  39. 39.
    Tallman, J.F., Thomas, J.W., and Gallager, D.W., 1978, GABAergic modulation of benzodiazepine binding site sensitivity, Nature, 274: 383–385.PubMedCrossRefGoogle Scholar
  40. 40.
    Török, K., Varga, V., Somogyi, J., Feuer, L., and Gulyás, J., 1981, Formation of γ-giutamyl-taurine in the rat brain, Neurosci. Lett., 27: 145–149.PubMedCrossRefGoogle Scholar
  41. 41.
    Varga, V., DeFeudis, F.V., Ossola, L., Geffard, M., and Mandel, P., 1980, Binding of muscimol and GABA in subfractions of crude membrane fraction of rat brain, Biochem. Pharmac, 29: 1077–1079.CrossRefGoogle Scholar
  42. 42.
    Varga, V., Török, K., Feuer, L., Gulyás, J., and Somogyi, J., 1985, Y-Glutamyltransferase in the brain and its role in formation of γ-L-glutamyl-taurine, in: “Progress in Clinical and Biological Research, Vol. 179, Taurine: Biological Actions and Clinical Perspectives”, S.S. Oja, L. Ahtee, P. Kontro and M. K. Paasonen, eds., Alan R. Liss, New York, pp. 115–125.Google Scholar
  43. 43.
    Whittaker, V.P., and Barker, L.A., 1972, The subcellular fractionation of brain tissue with special reference to the preparation of synaptosomes and their component organelles, in: “Methods of Neurochemistry, Vol. 2”, R. Fried, ed., Marcel Dekker, New York, pp. 1–52.Google Scholar
  44. 44.
    Zaczek, R., Koller, K., Cotter, R., Heller, D., and Coyle, J.T., 1983, N-Acetylaspartylglutamate: an endogenous peptide with high affinity for a brain “glutamate” receptor, Proc. Natl Acad. Sci. USA, 80: 1116–1119.PubMedCrossRefGoogle Scholar
  45. 45.
    Zukin, S.R., Young, A.B., and Snyder, S.H., 1974, Gamma-aminobutyric acid binding to receptor sites in the rat central nervous system, Proc. Natl Acad. Sci. USA, 71: 4802–4807.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • V. Varga
    • 1
    • 2
  • Kirsi-Marja Marnela
    • 1
  • Pirjo Kontro
    • 1
  • J. Gulyás
    • 3
  • Z. Vadász
    • 2
  • P. Lähdesmäki
    • 4
  • S. S. Oja
    • 1
  1. 1.Department of Biomedical SciencesUniversity of TampereTampereFinland
  2. 2.Institute of Biochemistry, Department ISemmelweis University Medical SchoolBudapestHungary
  3. 3.Institute of Organic ChemistryEötvös Lóránd UniversityBudapestHungary
  4. 4.Department of BiochemistryUniversity of OuluOuluFinland

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