Modulation of Glutamate and Gaba Release by Excitatory Amino Acid Receptor Agonists in Cultured Cerebellar Cells

  • G. Levi
  • V. Gallo
  • C. Giovannini
  • R. Suergiu
Part of the NATO ASI Series book series (volume 19)


The major excitatory input to the cerebellar cortex is represented by the mossy fibers, whose terminals form synaptic contacts with the granule cells dendrites (Palay and Chan—Palay 1974). It has been suggested that some of these fiber terminals use glutamate or aspartate as a transmitter (Kaneko et al. 1987). This proposal would be consistent with the presence of excitatory amino acid receptors on cerebellar granule cells, which was demonstrated both biochemically (Wroblewski et al. 1985; Nicoletti et al. 1986) and electrophysiologically (Cull—Candy and Ogden 1985).


Kainic Acid Cerebellar Granule Cell Kynurenic Acid Excitatory Amino Acid Receptor Aminooxyacetic Acid 
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  1. Abdel-latif AA (1986) Calcium-mobilizing receptors, phosphoinositides and the generation of second messengers, Pharmacol Rev 38: 227–272.PubMedGoogle Scholar
  2. Aloisi F, Ciotti MT, Levi G (1985) Characterization of GABAergic neurones in cerebellar primary cultures and selective neurotoxic effects of a serum fraction, J Neurosci 5: 2001–2008.PubMedGoogle Scholar
  3. Balcar VJ, Johnston GAR (1972) The structural specificity of the high affinity uptake of L-glutamate and Laspartate by rat brain slices, J Neurochem 19: 2657–2666.PubMedCrossRefGoogle Scholar
  4. Coleman PA, Massey SC, Miller RF (1986) Kynurenic acid distinguishes kainate and quisqualate receptors in the vertebrate retina, Brain Res 381: 172–175.PubMedCrossRefGoogle Scholar
  5. Cull-Candy SG, Ogden DC (1985) Ion channel activated by L-glutamate and GABA in cultured cerebellar neurones of the rat, Proc R Soc London B 224: 367–373.CrossRefGoogle Scholar
  6. Cull-Candy SG, Usowicz MM (1987) Multiple-conductance levels activated by excitatory amino acids in cerebellar neurons, Nature 325: 525–528.PubMedCrossRefGoogle Scholar
  7. Ferkany JW, Coyle JT (1982) Kainic acid selectively stimulates the release of endogenous excitatory acidic amino acids, J Pharmacol Exp Ther 225: 399–406.Google Scholar
  8. Ferkany JW, Zaczek R, Coyle JT (1982) Kainic acid stimulates excitatory amino acid neurotransmitter release at presynaptic receptors Nature 298: 757–759.Google Scholar
  9. Gallo V, Giovannini C., Levi G (1988) Expression of excitatory amino acid receptors and neurotransmitter amino acid release in cultured cerebellar neural cells, in Heuter G, ed., “Amino Acid Availability and Brain Function in Health and Disease”, Springer-Verlag, in press.Google Scholar
  10. Gallo V, Ciotti MT, Coletti A, Aloisi F, Levi G (1982) Selective release of glutamate from cerebellar granule cells differentiating in culture, Proc Natl Acad Sci USA 79: 7919–7923.PubMedCrossRefGoogle Scholar
  11. Gallo V, Suergiu R, Levi G (1986) Kainic acid stimulates GABA release from a subpopulation of cerebellar astrocytes, Eur J Pharmacol 133: 319–322.CrossRefGoogle Scholar
  12. Gallo V, Suergiu R, Levi G (1987a) Functional evaluation of glutamate receptor subtypes in cultured cerebellar neurones and astrocytes, Eur J Pharmacol 138: 293–297.PubMedCrossRefGoogle Scholar
  13. Gallo V, Suergiu R, Giovannini C, Levi G (1987b) Glutamate receptor subtypes in cultured cerebellar neurones: modulation of glutamate and GABA release, J Neurochem, in press.Google Scholar
  14. Halpain S, Wieczorek CM, Rainbow TC (1984) Localization of L-glutamate receptors in rat brain by quantitative autoradiography, J Neurosci 4: 2247–2258.PubMedGoogle Scholar
  15. Henke H, Beaudet A, Cuenod M (1981) Autoradiographic localization of specific kainic acid binding sites in pigeon and rat cerebellum, Brain Res 219: 95–105.PubMedCrossRefGoogle Scholar
  16. Ishida AT, Neyton J (1985) Quisqualate and L-glutamate inhibit retinal horizontal-cell responses to kainate, Proc Natl Acad Sci USA 82: 1837–1841.PubMedCrossRefGoogle Scholar
  17. Johnston GAR, Kennedy SME, Twitchin B (1979) Action of the neurotoxin kainic acid on high affinity uptake of L-glutamic acid in rat brain slices, J Neurochem 32: 121–127.PubMedCrossRefGoogle Scholar
  18. Kaneko T, Urade Y, Watanabe Y, Mizuno N (1987) Production, characterization, and immunohistochemical application of monoclonal antobodies to glutaminase purified from rat brain, J Neurosci 7: 302–309PubMedGoogle Scholar
  19. Levi G, Raiteri M (1976) Synaptosomal transport processes, Int Rev Neurobiol 19: 51–74.PubMedCrossRefGoogle Scholar
  20. Levi G, Wilkin GP, Ciotti MT, Johnstone SR (1983) Enrichment of differentiated stellate astrocytes in cerebellar interneuron cultures as studied by GFAP immunofluorescence and autoradiographic uptake patterns of H-D-aspartate and 3H-GABA, Dev Brain Res 10: 227–241.CrossRefGoogle Scholar
  21. Levi G, Aloisi F, Ciotti MT, Gallo V (1984) Autoradiographic localization and depolarization-induced release of acidic amino acids in differentiating cerebellar granule cell cultures, Brain Res 290: 77–86PubMedCrossRefGoogle Scholar
  22. Levi G, Gallo V, Ciotti MT (1986) Bipotential precursors of putative fibrous astrocytes and oligodendrocytes in rat cerebellar cultures express distinct surface features and “neuron-like” V-aminobutyric acid transport, Proc Natl Acad Sci USA 83: 1504–1508PubMedCrossRefGoogle Scholar
  23. London ED, Coyle JT (1979) Specific binding of 3H-kainic acid to receptor sites in rat brain, Molec Pharmacol 15, 492–505.Google Scholar
  24. McBean GJ, Robert PJ (1981) Glutamate-preferring receptors regulate the release of 3H-D-aspartate from rat hippocampal slices, Nature 291: 593–594.PubMedCrossRefGoogle Scholar
  25. Monaghan DT, Cotman CW (1982) The distribution of 3H-kainic acid binding sites in rat CNS as determined by autoradiography, Brain Res 252: 91–100.PubMedCrossRefGoogle Scholar
  26. Nicoletti F, Wroblewski JT, Novelli A, Alho H, Guidotti A, Costa E (1986) The activation of inositol phospholipid metabolism as a signal transducing system for excitatory amino acids in primary cultures of cerebellar granule cells, J Neurosci 6: 1905–1911.PubMedGoogle Scholar
  27. Palay SL, Chan-Palay V (1974) Cerebellar cortex. Cytology and organization, Springer-Verlag, Berlin.Google Scholar
  28. Pastuszko A, Wilson DF, Erecinska M (1984) Effects of kainic acid in rat brain synaptosomes: the involvement of calcium, J Neurochem 43: 747–754.PubMedCrossRefGoogle Scholar
  29. Pearce B, Dutton GR (1982) L-glutamate increases the spontaneous release of 3H-GABA from cultured cerebellar neurons, Dev Brain Res 3: 492–496.CrossRefGoogle Scholar
  30. Poli A, Contestabile A, Migani P, Rossi L, Rondelli C, Virgili M, Bissoli R, Bernabei O (1985) Kainic acid differentially affects the synaptosomal release of endogenous and exogenous amino acidic neurotransmitters, J Neurochem 45: 1677–1686.PubMedCrossRefGoogle Scholar
  31. Potashner SJ, Gerard D (1983) Kainate-enhanced release of 3H-D-aspartate from cerebral cortex and striatum: reversal by baclofen and pentobarbital, J Neurochem 40, 1548–1557.PubMedCrossRefGoogle Scholar
  32. Raff MC, Abney ER, Cohen J, Lindsay R, Noble M (1983b) Two types of astrocytes in cultures of developing rat white matter: differences in morphology, surface gangliosides and growth characteristics, J Neurosci 3: 1289–1300PubMedGoogle Scholar
  33. Slevin JT, Collins JF, Covle JT (1983) Analogue interactions with the brain receptor labeled by H-kainic acid, Brain Res 265: 169–172.PubMedCrossRefGoogle Scholar
  34. Unnerstall JR, Walmsley JK (1983) Autoradiographic localization of high- affinity 3H-kainic acid binding sites in rat forebrain, Eur J Pharmacol 86: 361–371.PubMedCrossRefGoogle Scholar
  35. Wilkin GP, Levi G, Johnstone S, Riddle PN (1983) Cerebellar astroglial cells in primary culture: Expression of different morphologica appearances and differential ability to take up 3H-D-aspartate and 3H-GABA, Dev Brain Res 10: 265–277CrossRefGoogle Scholar
  36. Wroblewski JT, Nicoletti F, Costa E, (1985) Different coupling of excitatory amino acid receptors with Ca2+ channels in primary cultures of cerebellar granule cells, Neuropharmacology 24: 919–921.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • G. Levi
    • 1
  • V. Gallo
    • 1
  • C. Giovannini
    • 1
  • R. Suergiu
    • 1
  1. 1.Istituto Superiore di SanitàLaboratorio di Fisiopatologia di Organo e di SistemaRomaItaly

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