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Neuromodulatory Actions of Glutamate, GABA and Taurine: Regulatory Role of Astrocytes

  • Arne Schousboe
  • Orla M. Larsson
  • Aase Frandsen
  • Bo Belhage
  • Herminia Pasantes-Morales
  • Povl Krogsgaard-Larsen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 296)

Abstract

In addition to being actively involved in the general metabolism of the central nervous system, the amino acids glutamate and Chapter 16(173,175–176)-aminobutyrate (GABA) serve as respectively excitatory and inhibitory neurotransmitters (Schousboe, 1990). This function is mediated by pharmacologically distinct receptors for each of the two amino acids. Receptors for glutamate are generally subdivided into 3 major classes exhibiting different pharmacological profiles, i.e. N-methyl-D-aspartate-(NMDA), kainate-, and quisqualate/AMPA (RS-α-amino-3-hydraxy-5-methyl-4-isoxazolo-propionate)- receptors (Watkins and Olverman, 1987). Likewise, GABA receptors are subdivided into two major classes referred to as GABAA and GABAB receptors (Johnston et al., 1984). It should, however, be emphasized that diversities exist within these respective classes of receptors as binding sites with different affinities for the amino acids have been observed (Johnston et al., 1984; Drejer & Honoré, 1988). Such a diversity is consistent with the discovery of a large number of subunits of these receptors with different amino acid sequences (Schofield et al., 1987; Hollmann et al., 1989). This, in turn, may be reflected by the multiple functions of these receptors such as involvement in modulation of neuro-transmitter release and mediation of trophic and toxic actions. These functional aspects will be discussed below.

Keywords

Glutamate Receptor Excitatory Amino Acid Gaba Receptor Cerebellar Granule Cell Glutamate Uptake 
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. Abraham, J.H. and Schousboe, A., 1989, Effects of taurine on cell morphology and expression of lew-affinity GABA receptors in cultured cerebellar granule cells. Neurochenu Res. 14:1031.CrossRefGoogle Scholar
  2. Belhage, B., Meier, E., and Schousboe, A., 1986, GABA-agonists induce the formation of low-affinity GABA-receptors on cultured cerebellar granule cells via preexisting high affinity GABA receptors. Neurochem. Res. 11:599.PubMedCrossRefGoogle Scholar
  3. Belhage, B., Hansen, G.H., Meier, E. and Schousboe, A., 1990a, Effects of inhibitors of protein synthesis and intracellular transport on the GABA-agonist induced functional differentiation of cultured cerebellar granule cells. J. Neurochem. 55:1107.PubMedCrossRefGoogle Scholar
  4. Belhage, B., Hansen, G.H. and Schousboe, A., 1990b, GABA agonist induced changes in ultrastructure and GABA receptor expression in cerebellar granule cells is linked to hyperpolarization of the neurons. Int. J. Devl. Neurosci. 8:473.CrossRefGoogle Scholar
  5. Benveniste, H., Drejer, J., Schousboe, A., and Diemer, N.H., 1984, Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J. Neurochem. 43:1369.PubMedCrossRefGoogle Scholar
  6. Bouchelouche, P., Belhage, B., Frandsen, A., Drejer, J., and Schousboe, A., 1989, Glutamate receptor activation in cultured cerebellar granule cells increases cytosolic free Ca2+ by mobilization of cellular Ca2+ and activation of Ca influx. Exp. Brain Res. 76:281.PubMedCrossRefGoogle Scholar
  7. Choi, D.W., 1988, Glutamate neurotoxicity and diseases of the nervous system. Neuron 1:623.PubMedCrossRefGoogle Scholar
  8. Choi, D.W., Maulucci-Gedde, M.A., and Kriegstein, A.R., 1987, Glutamate neurotoxicity in cortical cell culture. J. Neurosci. 7:357.PubMedGoogle Scholar
  9. Choi, D.W., Koh, J., and Peters, S., 1988, Pharmacology of glutamate neurotoxicity in cortical cell culture: Attenuation by NMDA antagonists. J. Neurosci. 8:185.PubMedGoogle Scholar
  10. Davies, S.N., Fletcher, E.J., and Lodge, D., 1988, Evidence for a fourth glutamate receptor subtype on rat central neurones in vivo and in vitro. J. Physiol. 406:15P.Google Scholar
  11. Debler, E.A., and Lajtha, A., 1987, High-affinity transport of γ-aminofcutyric acid, glycine, taurine, L-aspartic acid, and L-glutamic acid in synaptosomal (P2) tissue: A kinetic and substrate specificity analysis. J. Neurochem. 48:1851.PubMedCrossRefGoogle Scholar
  12. Drejer, J., and Honoré, T., 1988, Excitatory amino acid receptors, in: “Glutamine and Glutamate in Mammals,” E. Kvamme, ed., Volume 2, CRC Press, FL, 89.Google Scholar
  13. Drejer, J., Meier, E., and Schousboe, A., 1983, Novel neuron-related regulatory mechanisms for astrocytic glutamate and GABA high affinity uptake. Neurosci. Lett. 37:301.PubMedCrossRefGoogle Scholar
  14. Drejer, J., Benveniste, H., Diemer, N.H., and Schousboe, A., 1985, Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro. J. Neurochem. 45:145.PubMedCrossRefGoogle Scholar
  15. Drejer, J., Honoré, T., Meier, E., and Schousboe, A., 1986, Pharmacologically distinct glutamate receptors on cerebellar granule cells. Life Sci. 38:2077.PubMedCrossRefGoogle Scholar
  16. Drejer, J., Honoré, T., and Schousboe, A., 1987, Excitatory amino acid-induced release of 3H-GABA from cultured mouse cerebral cortex interneurons. J. Neurosci. 7:2910.PubMedGoogle Scholar
  17. Dunlop, J., Grieve, A., Schousboe, A., and Griffiths, R., 1989, Neuroactive sulphur amino acids evoke a calcium-dependent transmitter release from cultured neurones that is sensitive to excitatory amino acid receptor antagonists. J. Neurochem. 52:1648.PubMedCrossRefGoogle Scholar
  18. Dunlop, J., Grieve, A., Schousboe, A., and Griffiths, R., 1990, Characterization of the receptor-mediated sulphur amino acid-evoked release of [3H]D-aspartate from primary cultures of cerebellar granule cells. Neurochem. Int. 16:119.PubMedCrossRefGoogle Scholar
  19. Frandsen, A., and Schousboe, A., 1987, Time and concentration dependency of the toxicity of excitatory amino acids on cerebral neurones in primary culture. Neurochem. Int. 10:583.PubMedCrossRefGoogle Scholar
  20. Frandsen, A. and Schousboe, A., 1990, Development of excitatory amino acid induced cytotoxicity in cultured neurones. Int. J. Devl. Neurosci., 8:209.CrossRefGoogle Scholar
  21. Frandsen, A., Drejer, J., and Schousboe, A., 1989a, Direct evidence that excitotoxicity in cultured neurons is mediated via N-methyl-D-aspartate (NMDA) as well as non-NMDA receptors. J. Neurochem. 53:297.PubMedCrossRefGoogle Scholar
  22. Frandsen, A., Drejer, J., and Schousboe, A., 1989b, Glutamate-induced 45Ca2+ uptake into immature cerebral cortex neurons shows a distinct pharmacological profile. J. Neurochem. 53:1959.PubMedCrossRefGoogle Scholar
  23. Frandsen, A., Krogsgaard-Larsen, P. and Schousboe, A., 1990a, Novel glutamate receptor antagonists selectively protect against kainic acid neurotoxicity in cultured cerebral cortex neurons. J. Neurochem. 55: in press.Google Scholar
  24. Frandsen, A., Quistorff, B. and Schousboe, A., 1990b, Phenobarbital protects cerebral cortex neurones against toxicity induced by kainate but not by other excitatory amino acids. Neurosci. Lett. 11:233.CrossRefGoogle Scholar
  25. Gallo, V., Suergiu, R., Giovannini, C., and Levi, G., 1987, Glutamate receptor subtypes in cultured cerebellar neurons: Modulation of glutamate and 7-aminobutyric acid release. J. Neurochem. 49: 1801.PubMedCrossRefGoogle Scholar
  26. Gallo, V., Suergiu, R., Giovannini, C., and Levi, G., 1989, Expression of excitatory amino acid receptors by cerebellar cells of the type-2 astrocyte cell lineage. J. Neurochem. 52:1.PubMedCrossRefGoogle Scholar
  27. Gonsalves, S.F., Twitchell, B., Harbaugh, R.E., Krogsgaard-Larsen, P., and Schousboe, A., 1989a, Anticonvulsant activity of intracerebroventricularly administered glial GABA uptake inhibitors and other GABAmimetics in chemical seizure models. Epilepsy Res. 4:34.PubMedCrossRefGoogle Scholar
  28. Gonsalves, S.F., Twitchell, B., Harbaugh, R.E., Krogsgaard-Larsen, P., and Schousboe, A., 1989b, Anticonvulsant activity of the glial GABA uptake inhibitor, THAO, in chemical seizures. Eur. J. Pharmacol. 168:265.PubMedCrossRefGoogle Scholar
  29. Greenamyre, J.T., Higgins, D.S., Young, A.B., and Penney, J.B., 1990, Regional ontogeny of a unique glutamate recognition site in rat brain: An autoradiographic study. Int. J. Devl. Neurosci. 8:437.CrossRefGoogle Scholar
  30. Guldner, F.H., and Wolff, J.R., 1973, Neuron-glial synaptoid contacts of the median eminence of the rat: Ultrastructure, staining properties, and distribution on tanycytes. Brain Res. 61:217.PubMedCrossRefGoogle Scholar
  31. Hansen, A.J., 1978, The extracellular potassium concentration in brain cortex following ischemia in hypo- and hyperglycemic rats. Acta Physiol. Scand. 102:324.PubMedCrossRefGoogle Scholar
  32. Holopainen, I., and Kontro, P., 1986, High-affinity uptake of taurine and β-alanine in primary cultures of rat astrocytes. Neurochem. Res. 11:207.PubMedCrossRefGoogle Scholar
  33. Hollmann, M., O’Shear-Greenfield, A., Rogers, S.W., and Heinemann, S., 1989, Cloning by functional expression of a member of the glutamate receptor family. Nature 342:643.PubMedCrossRefGoogle Scholar
  34. Honoré, T., Davis, S.N., Drejer, J., Fletcher, J.E., Jacobsen, P., Lodge, D., and Nielsen, F.E., 1988, Quinoxalinediones: Potent competitive non-NMDA glutamate receptor antagonists. Science 241:701.PubMedCrossRefGoogle Scholar
  35. Huxtable, R.J., 1989, Taurine in the central nervous system and the mammalian actions of taurine. Prog. Neurobiol. 32:471.PubMedCrossRefGoogle Scholar
  36. Johnston, G.A.R., Allan, R.D., and Skerritt, J.H., 1984, GABA receptors, in: “Handbook of Neurochemistry, 2nd. Edition, Vol. 6,” A. Lajtha, ed., Plenum Press, New York, 213.Google Scholar
  37. Krogsgaard-Larsen, P., Falch, E., Larsson, O.M., and Schousboe, A., 1987, GABA uptake inhibitors: Relevance to antiepileptic drug research. Epilepsy Res. 1:77.PubMedCrossRefGoogle Scholar
  38. Krogsgaard-Larsen, P., Ferkany, J.W., Nielsen, E.O., Madsen, U., Ebert, B., Johansen, J.S., Diemer, N.H., Bruhn, T., Beattie, D.T., and Curtis, D.R., 1990, Novel class of antagonists at non-N-methyl-D-aspartic acid excitatory amino acid receptors. Synthesis, in vitro and in vivo pharmacology and neuroprotection. J. Med. Chem., in press.Google Scholar
  39. Larsson, O.M., Griffiths, R., Allan, I.C., and Schousboe, A., 1986, Mutual inhibition kinetic analysis of γ-aminobutyric acid, taurine and β-alanine high affinity transport into neurons and astrocytes: evidence for similarity between the taurine and β-alanine carriers in both cell types. J. Neurochem. 47:426.PubMedCrossRefGoogle Scholar
  40. Lehmann, A., Hagberg, H., and Hamberger, A., 1984, A role for taurine in the maintenance of homeostasis in the central nervous system during hyperexcitation? Neurosci. Lett. 52:341.PubMedCrossRefGoogle Scholar
  41. Meier, E., and Schousboe, A., 1982, Differences between GABA receptor binding to membranes from cerebellum during postnatal development and from cultured cerebellar granule cells. Dev. Neurosci. 5:546.PubMedCrossRefGoogle Scholar
  42. Meier, E., Drejer, J., and Schousboe, A., 1984, GABA induces functionally active lew-affinity GABA receptors on cultured cerebellar granule cells. J. Neurochem. 43:1737.PubMedCrossRefGoogle Scholar
  43. Pasantes-Morales, H., and Schousboe, A., 1988, Volume regulation in astrocytes: A role for taurine as an osmoeffector. J. Neurosci. Res. 20:505.CrossRefGoogle Scholar
  44. Pasantes-Morales, H., and Schousboe, A., 1989, Release of taurine from astrocytes during potassium-evoked swelling. Glia 2:45.PubMedCrossRefGoogle Scholar
  45. Pasantes-Morales, H., Morán, J., and Schousboe, A., 1990, Volume-sensitive release of taurine from cultured astrocytes: Properties and mechanism. Glia 3: in press.Google Scholar
  46. Pin, J.-P., and Bockaert, J., 1989, Two distinct mechanisms, differentially affected by excitatory amino acids, trigger GABA release from fetal mouse striatal neurons in primary culture. J. Neurosci. 9:648.PubMedGoogle Scholar
  47. Pin, J.-P., Van-Vliet, B.J., and Bockaert, J., 1988, NMDA- and Kainate-evoked GABA release from striatal neurones differentiated in primary culture: Differential blocking by phencyclidine. Neurosci. Lett. 87:87.PubMedCrossRefGoogle Scholar
  48. Rothman, S., 1984, Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death. J. Neurosci. 4:1884.PubMedGoogle Scholar
  49. Rothman, S., and Olney, J.W., 1986, Glutamate and the pathophysiology of hypoxic ischemic brain damage. Ann. Neurol. 19:105.PubMedCrossRefGoogle Scholar
  50. Sandberg, S., Butcher, S.P., and Hagberg, H., 1986, Extracellular overflew of neuroactive amino acids during severe insulin-induced hypoglycemia in vivo dialysis of the rat hippocaitpus. J. Neurochem. 47:178.PubMedCrossRefGoogle Scholar
  51. Schofield, P.R., Darlison, M.G., Fujita, N., Burt, D.R., Stephenson, F.A., Rodriguez, H., Rhee, L.M., Ramachandran, J., Reale, V., Glencorse, T.A., Seeburg, P.H., and Barnard, E.A., 1987, Sequence and functional expression of the GAEA receptor show a ligand-gated receptor superfamily. Nature 328:221.PubMedCrossRefGoogle Scholar
  52. Schousboe, A., 1979, Effects of GABA-analogues on the high-affinity uptake of GABA in astrocytes in primary cultures, in: “GABA-Biochemistry and CNS Functions,” P. Mandel, and DeFeudis, F.V., eds., Plenum Publ. Corp., New York, 219.Google Scholar
  53. Schousboe, A., 1981, Transport and metabolism of glutamate and GABA in neurons and glial cells. Int. Rev. Neurobiol. 22:1.PubMedCrossRefGoogle Scholar
  54. Schousboe, A., 1982, Metabolism and function of neurotransmitters, in: “Neuroscience Approached through Cell Culture, Vol. 1,” S.E. Pfeiffer, ed., CRC Press, Boca Raton, FL, 108.Google Scholar
  55. Schousboe, A., 1990, Neurochemical alterations associated with epilepsy or seizure activity, in: “Comprehensive Epileptology,” M. Dam, and Gram, L., eds., Raven Press, New York, 1.Google Scholar
  56. Schousboe, A., and Divac, I., 1979, Differences in glutamate uptake in astrocytes cultured frati different brain regions. Brain Res. 177:407.PubMedCrossRefGoogle Scholar
  57. Schousboe, A., Larsson, O.M., Krogsgaard-Larsen, P., Drejer, J., and Hertz, L., 1988, Uptake and release processes for neurotransmitter amino acids in astrocytes, in: “The Biochemical Pathology of Astrocytes,” M.D. Norenberg, Hertz, L., and Schousboe, A., eds., Alan R. Liss, New York, 381.Google Scholar
  58. Schousboe, A., Frandsen, A., and Drejer, J., 1989, Evidence for evoked release of adenosine and glutamate from cultured cerebellar granule cells. Neurochem. Res., 14:871.PubMedCrossRefGoogle Scholar
  59. Schousboe, A., Sanchez-Olea, R., and Pasantes-Morales, H., 1990a, Depolarization induced neuronal release of taurine in relation to synaptic transmission: Comparison with GABA and glutamate, in: “Functional Neurochemistry of Taurine,” H. Pasantes-Morales, Shain, W., Martin D.L., and del Rio, R.M., eds., Alan R. Liss, New York, 289.Google Scholar
  60. Schousboe, A., Krogsgaard-Larsen, P., Larsson, O.M., Gonsalves, S.F., Harbaugh, R.E., and Wood, J.D., 1990b, GABA uptake inhibitors: Possible use as anti-epileptic drugs, in: “Amino Acids, Chemistry, Biology and Medicine,” G. Lubec, and Rosenthal, G.A., eds., ESCOM Science Publishers B.V., Leiden, 345.Google Scholar
  61. Schousboe, A., Moran, J., and Pasantes-Morales, H., 1990c, Potassium-stimulated release of taurine from cultured cerebellar granule neurons is associated with cell swelling. J. Neurosci. Res., in press.Google Scholar
  62. Sheardown, M.J., Nielsen, E.Ø., Hansen, A.J., Jacobsen, P., and Honoré, T., 1990, 2,3-Dihydroxy-6-nitro-γ-sulphamoyl-benzo(F)quinoxaline: A neurqprotectant for cerebral ischemia. Science 247:571.PubMedCrossRefGoogle Scholar
  63. Tapia, R., 1975, Biochemical Pharmacology of GABA in CNS, in: “Handbook of Psychoqpharmacology, Vol. 4,” L.L. Iversen, Iversen, S.D., and Snyder S.H., eds., Plenum Publ. Corp., New York, 1.Google Scholar
  64. Wahl, P., Schousboe, A., Honoré, T., and Drejer, J., 1989, Glutamate-induced increase in intracellular Ca2+ in cerebral cortex neurons is transient in immature cells but permanent in mature cells. J. Neurochem. 53:1316.PubMedCrossRefGoogle Scholar
  65. Watkins, J.C., and Olverman, H.J., 1987, Agonists and antagonists for excitatory amino acid receptors. Trends Neurosci. 10:265.CrossRefGoogle Scholar
  66. Weiss, S., 1988, Excitatory amino acid-evoked release of gamma-[3H]- aminobutyric acid from striatal neurones in primary culture. J. Neurochem. 51:435.PubMedCrossRefGoogle Scholar
  67. Westergaard, N., Fosmark, H., and Schousboe, A., 1991, Metabolism and release of glutamate in cerebellar granule cells cocultured with astrocytes from cerebellum or cerebral cortex. J. Neurochem. 56: in press.Google Scholar
  68. Wood, J.D., 1975, The role of γ-aminobutyric acid in the mechanism of seizures. Prog. Neurobiol. 5:79.CrossRefGoogle Scholar

Copyright information

© Current Medicine, Inc. 2004

Authors and Affiliations

  • Arne Schousboe
    • 1
  • Orla M. Larsson
    • 1
  • Aase Frandsen
    • 1
  • Bo Belhage
    • 2
  • Herminia Pasantes-Morales
    • 3
  • Povl Krogsgaard-Larsen
    • 4
  1. 1.PharmaBiotec Research Center, Dept. of BiologyRoyal Danish School of PharmacyCopenhagenDenmark
  2. 2.Dept. of Biochemistry APanum InstituteCopenhagenDenmark
  3. 3.Inst. of Cellular PhysiologyNational Univ. of MexicoMexico D.F.Mexico
  4. 4.PharmaBiotec Research Center, Dept. of Organic ChemistryRoyal Danish School of PharmacyCopenhagenDenmark

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