Neurochemical Research

, Volume 28, Issue 2, pp 347–352 | Cite as

Role of Astrocytes in the Maintenance and Modulation of Glutamatergic and GABAergic Neurotransmission

  • Arne Schousboe


The functional activity in the brain is primarily composed of an interplay between excitation and inhibition. In any given region the output is based upon a complex processing of incoming signals that require both excitatory and inhibitory units. Moreover, these units must be regulated and balanced such that an integrated and finely tuned response is generated. In each of these units or synapses the activity depends on biosynthesis, release, receptor interaction, and inactivation of the neurotransmitter in question; thus, it is easily understood that each of these processes needs to be highly regulated and controlled. It is interesting to note that in case of the most prevailing neurotransmitters, glutamate and GABA, which mediate excitation and inhibition, respectively, the inactivation process is primarily maintained by highly efficient, high-affinity transport systems capable of maintaining transmembrane concentration gradients of these amino acids of 104–105-fold. The demonstration of the presence of transporters for glutamate and GABA in both neuronal and astrocytic elements naturally raises the question of the functional importance of the astrocytes in the regulation of the level of the neurotransmitters in the synaptic cleft and hence for the activity of excitatory and inhibitory neurotransmission. Obviously, this discussion has important implications for the understanding of the role of astrocytes in disease states in which imbalances between excitation and inhibition are a triggering factor, for example, epilepsy and neurodegeneration.

Epilepsy neurodegeneration glia neurons GABA-transporters glutamate-transporters 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Logan, W. J. and Snyder, S. H. 1972. High affinity uptake systems for glycine, glutamic and aspartic acids in synaptosomes of rat central nervous tissues. Brain Res. 42:413–431.PubMedGoogle Scholar
  2. 2.
    Henn, F. A. and Hamberger, A. 1971. Glial cell function: uptake of transmitter substances. Proc. Natl. Acad. Sci. USA 68:2686–2690.PubMedGoogle Scholar
  3. 3.
    Henn, F. A., Goldstein, M. N., and Hamberger, A. 1974. Uptake of the neurotransmitter candidate glutamate by glia. Nature 249:663–664.PubMedGoogle Scholar
  4. 4.
    Schousboe, A., Hertz, L., and Svenneby, G. 1977. Uptake and metabolism of GABA in astrocytes cultured from dissociated mouse brain hemispheres. Neurochem. Res. 2:217–229.Google Scholar
  5. 5.
    Schousboe, A., Svenneby, G., and Hertz, L. 1977. Uptake and metabolism of glutamate in astrocytes cultured from dissociated mouse brain hemispheres. J. Neurochem. 29:999–1005.PubMedGoogle Scholar
  6. 6.
    Hertz, L., Schousboe, A., Boechler, N., Mukerji, S., and Fedoroff, S. 1978. Kinetic characteristics of the glutamate uptake into normal astrocytes in cultures. Neurochem. Res. 3:1–14.Google Scholar
  7. 7.
    Danbolt, N. C. 1994. The high-affinity uptake system for excitataory amino acids in the brain. Prog. Neurobiol. 44:377–396.PubMedGoogle Scholar
  8. 8.
    Danbolt, N. C. 2001. Glutamate uptake. Progr. Neurobiol. 65:1–105.PubMedGoogle Scholar
  9. 9.
    Guastella, J., Nelson, N., Nelson, H., Czyzyk, L., Keynan, S., Miedel, M. C., Davidson, N., Lester, H. A., and Kanner, B. I. 1990. Cloning and expression of a rat brain GABA transporter. Science 249:1303–1306.PubMedGoogle Scholar
  10. 10.
    Blakely, R. D., Berson, H. E., Fremeau, R. T., Caron, M. G., Peek, M. M., Prince, H. K., and Bradley, C. C. 1991. Cloning and expression of a functional serotonin transporter from rat brain. Nature 354:66–70.PubMedGoogle Scholar
  11. 11.
    Kilty, J., Lorang, D., and Amara, S. G. 1991. Cloning and expression of a cocaine-sensitive dopamine transporter. Science 254:578–579.PubMedGoogle Scholar
  12. 12.
    Storck, T., Schulte, S., Hofmann, K., and Stoffel, W. 1992. Structure, expression, and functional analysis of a Na+-dependent glutamate/aspartate transporter from rat brain. Proc. Natl. Acad. Sci. USA 89:10955–10959.PubMedGoogle Scholar
  13. 13.
    Pines, G., Danbolt, N. C., Bjorås, M., Zhang, Y., Bendahan, A., Eide, L., Koepsell, H., Storm-Mathisen, J., Seeberg, E., and Kanner, B. I. 1992. Cloning and expression of a rat brain L-glutamate transporter. Nature 360:464–467.PubMedGoogle Scholar
  14. 14.
    Kanai, Y. and Hediger, M. A. 1992. Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360:467–471.PubMedGoogle Scholar
  15. 15.
    Fairman, W. A., Vandenberg, R. J., Arriza, J. L., Kavanaugh, M. P., and Amara, S. G. 1995. An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature 375:599–603.PubMedGoogle Scholar
  16. 16.
    Arriza, J. L., Eliasof, S., Kavanaugh, M. P., and Amara, S. G. 1997. Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc. Natl. Acad. Sci. USA 94:4155–4160.PubMedGoogle Scholar
  17. 17.
    Gegelashvili, G. and Schousboe, A. 1998. Cellular distribution and kinetic properties of high-affinity glutamate transporters. Brain Res. Bull. 45:233–238.PubMedGoogle Scholar
  18. 18.
    Lehre, K. P., Levy, L. M., Ottersen, O. P., Storm-Mathisen, J., and Danbolt, N. C. 1995. Differential expression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations. J. Neurosci. 15:1835–1853.PubMedGoogle Scholar
  19. 19.
    Lehre, K. P. and Danbolt, N. C. 1998. The number of glutamate transporter subtype molecules at glutamatergic synapses: chemical and stereological quantification in young adult rat brain. J. Neurosci. 18:8751–8757.PubMedGoogle Scholar
  20. 20.
    Levy, L. M. 2002. Structure, function and regulation of glutamate transporters. Pages 307–336, in Egebjerg, J., Schousboe, A., and Krogsgaard-Larsen, P. (eds.), Glutamate and GABA Receptors and Transporters. Structure, Function and Pharmacology, Taylor and Francis, London.Google Scholar
  21. 21.
    Northington, F. J., Traystman, R. J., Koehler, R. C., and Martin, L. J. 1999. GLT1, glial glutamate transporter, is transiently expressed in neurons and develops astrocyte specificity only after midgestation in the bovine fetal brain. J. Neurobiol. 39:515–526.PubMedGoogle Scholar
  22. 22.
    Plachez, C., Danbolt, N. C., and Recasens, M. 2000. Transient expression of the glial glutamate transporters GLAST and GLT in hippocampal neurons in primary culture. J. Neurosci. Res. 59:587–593.PubMedGoogle Scholar
  23. 23.
    Rothstein, J. D., Martin, L., Levey, A. I., Dykes-Hoberg, M., Jin, L., Wu, D., Nash, N., and Kuncl, R. W. 1994. Localization of neuronal and glial glutamate transporters. Neuron 13:713–725.PubMedGoogle Scholar
  24. 24.
    Hertz, L. 1979. Functional interactions between neurons and astrocytes: I. Turnover and metabolism of putative amino acid transmitters. Prog. Neurobiol. 13:277–323.PubMedGoogle Scholar
  25. 25.
    Schousboe, A. 1981. Transport and metabolism of glutamate and GABA in neurons and glial cells. Int. Rev. Neurobiol. 22:1–45.PubMedGoogle Scholar
  26. 26.
    Yamada, K., Watanabe, M., Shibata, T., Tanaka, K., Wada, K., and Inoue, Y. 1996. EAAT4 is a post-synaptic glutamate transporter at Purkinje cell synapses. Neuroreport 7:2013–2017.PubMedGoogle Scholar
  27. 27.
    Dehnes, Y., Chaudhry, F. A., Ullensvang, K., Lehre, K. P., Storm-Mathisen, J., and Danbolt, N. C. 1998. The glutamate transporter EAAT4 in rat cerebellar Purkinje cells: a glutamate-gated chloride channel concentrated near the synapse in parts of the dendritic membrane facing astroglia. J. Neurosci. 18:3606–3619.PubMedGoogle Scholar
  28. 28.
    Rauen, T., Fischer, F., and Wiessner, M. 1999. Glia-neuron interaction by high-affinity glutamate transporters in neurotransmission. Adv. Exp. Med. Biol. 468:81–95.PubMedGoogle Scholar
  29. 29.
    Tong, G. and Jahr, C. E. 1994. Block of glutamate transporters potentiates postsynaptic excitation. Neuron 13:1195–1203.PubMedGoogle Scholar
  30. 30.
    Wadiche, J. I., Arriza, J. L., Amara, S. G., and Kavanaugh, M. P. 1995. Kinetics of a human glutamate transporter. Neuron 14:1019–1027.PubMedGoogle Scholar
  31. 31.
    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. 43:1369–1374.PubMedGoogle Scholar
  32. 32.
    Hagberg, H., Lehmann, A., Sandberg, M., Nyström, B., Jacobsen, I., and Hamberger, A. 1985. Ischemia-induced shift of inhibitory and excitatory amino acids from intra-to extracellular compartments. J. Cereb. Blood Flow Metab. 5:413–419.PubMedGoogle Scholar
  33. 33.
    Sandberg, M., Butcher, S. P., and Hagberg, H. 1986. Extracellular overflow of neuroactive amino acids during severe insulin-induced hypoglycemia: in vivo dialysis of rat hippocampus. J. Neurochem. 47:178–184.PubMedGoogle Scholar
  34. 34.
    Gegelashvili, G. and Schousboe, A. 1997. High-affinity glutamate transporters: regulation of expression and activity. Mol. Pharmacol. 52:6–15.PubMedGoogle Scholar
  35. 35.
    Gegelashvili, G., Robinson, M. B., Trotti, D., and Rauen, T. 2001. Regulation of glutamate transporters in health and disease. Prog. Brain Res. 132:267–286.PubMedGoogle Scholar
  36. 36.
    Rothstein, J. D., Van Kammen, M., Levey, A. I., Martin, L. J., and Kuncl, R. W. 1995. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann. Neurol. 38:73–84.PubMedGoogle Scholar
  37. 37.
    Choi, D. W. and Rothman, S. M. 1990. The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu. Rev. Neurosci. 13:171–182.PubMedGoogle Scholar
  38. 38.
    Schousboe, A. and Frandsen, A. 1995. Glutamate receptors and neurotoxicity. Pages 239–251, in Stone, T. W. (ed.), CNS Neurotransmitters and Neuromodulators: Glutamate, CRC Press, Boca Raton, FL.Google Scholar
  39. 39.
    Wang, G. J., Chung, H. J., Schnuer, J., Pratt, K., Zable, A. C., Kavanaugh, M. P., and Rosenberg, P. A. 1998. High affinity glutamate transport in rat cortical neurons in culture. Mol. Pharmacol. 53:88–96.PubMedGoogle Scholar
  40. 40.
    Chen, W., Aoki, C., Mahadomrongkul, V., Gruber, C. E., Wang, G. J., Blitzblau, R., Irwin, N., and Rosenberg, P. A. 2002. Expression of a variant form of the glutamate transporter GLT1 in neuronal cultures and in neurons and astrocytes in the rat brain. J. Neurosci. 22:2142–2152.PubMedGoogle Scholar
  41. 41.
    Drejer, J., Meier, E., and Schousboe, A. 1983. Novel neuron-related regulatory mechanisms for astrocytic glutamate and GABA high affinity uptake. Neurosci. Lett. 37:301–306.PubMedGoogle Scholar
  42. 42.
    Gegelashvili, G., Danbolt, N. C., and Schousboe, A. 1997. Neuronal soluble factors differentially regulate the expression of the GLT1 and GLAST glutamate transporters in cultured astroglia. J. Neurochem. 69:2612–2615.PubMedGoogle Scholar
  43. 43.
    Swanson, R. A., Liu, J., Miller, J. W., Rothstein, J. D., Farrel, K., Stein, B. A., and Longuemare, M. C. 1997. Neuronal regulation of glutamate transporter subtype expression in astrocytes. J. Neurosci. 17:932–940.PubMedGoogle Scholar
  44. 44.
    Schlag, B. D., Vondrasek, J. R., Munir, M., Kalandadze, A., Zelenaia, O. A., Rothstein, J. D., and Robinson, M. B. 1998. Regulation of the glial Na+-dependent glutamate transporters by cyclic AMP analogs and neurons. Mol. Pharmacol. 53:355–369.PubMedGoogle Scholar
  45. 45.
    Gegelashvili, G., Civenni, G., Racagni, G., Danbolt, N. C., Schousboe, I., and Schousboe, A. 1996. Glutamate receptor agonists up-regulate glutamate transporter glast in astrocytes. Neuroreport 8:261–265.PubMedGoogle Scholar
  46. 46.
    Gegelashvili, G., Dehnes, Y., Danbolt, N. C., and Schousboe, A. 2000. The high-affinity glutamate transporters GLT1, GLAST, and EAAT4 are regulated via different signalling mechanisms. Neurochem. Int. 37:163–170.PubMedGoogle Scholar
  47. 47.
    Dowd, L. A. and Robinson, M. B. 1996. Rapid stimulation of EAAC1–mediated Na+-dependent L-glutamate transport activity in C6 glioma cells by phorbol ester. J. Neurochem. 67:508–516.PubMedGoogle Scholar
  48. 48.
    Gonsalez, M. I. and Ortega, A. 1997. Regulation of the Na+-dependent high affinity glutamate/aspartate transporter in cultured Bergmann glia by phorbol esters. J. Neurosci. Res. 50:585–590.PubMedGoogle Scholar
  49. 49.
    Gonsalez, M. I., Lopez-Colome, A. M., and Ortega, A. 1999. Sodium-dependent glutamate transport in Müller glial cells: regulation by phorbol esters. Brain Res. 831:140–145.PubMedGoogle Scholar
  50. 50.
    Davis, K. E., Sraff, D. J., Weinstein, E. A., Bannermann, P. G., Correale, D. M., Rothstein, J. D., and Robinson, M. B. 1998. Multiple signaling pathways regulate cell surface expression and activity of the excitatory amino acid carrier 1 subtype of Glu transporter in C6 glioma. J. Neurosci. 18:2475–2485.PubMedGoogle Scholar
  51. 51.
    Schousboe, A. and Kanner, B. 2002. GABA transporters: functional and pharmacological properties. Pages 337–349, in Egebjerg, J., Schousboe, A., and Krogsgaard-Larsen, P. (eds.), Glutamate and GABA Receptors and Transporters, Taylor & Francis Publ., London, UK.Google Scholar
  52. 52.
    Schousboe, A. and Westergaard, N. 1995. Transport of neuro-active amino acids in astrocytes. Pages 246–258, in Kettenmann, H. and Ransom, B. (eds.), Neuroglia, Oxford University Press, New York.Google Scholar
  53. 53.
    Hertz, L. and Schousboe, A. 1987. Primary cultures of GABA-ergic and glutamatergic neurons as model systems to study neurotransmitter functions: I. Differentiated cells. Pages 19–31, in Vernadakis, A., Privat, A., Lauder, J. M., Timiras, P. S., and Giacobini, E. (eds.), Model Systems of Development and Aging of the Nervous System, M. Nijhoff Publ. Comp., Boston, MD.Google Scholar
  54. 54.
    Gram, L., Larsson, O. M., Johnsen, A. H., and Schousboe, A. 1988. Effects of valproate, vigabatrin and amino oxyacetic acid on release of endogenous and exogenous GABA from cultured neurons. Epilepsy Res. 2:87–95.PubMedGoogle Scholar
  55. 55.
    Minelli, A., DeBiasi, S., Brecha, N. C., Zuccarello, L. V., and Conti, F. 1996. GAT-3, a high-affinity GABA plasma membrane transporter, is localized to astrocytic processes, and is not confined to the vicinity of GABAergic synapses in the cerebral cortex. J. Neurosci. 16:6255–6264.PubMedGoogle Scholar
  56. 56.
    Ribak, C. E., Tong, W. M., and Brecha, N. C. 1996. GABA plasma membrane transporters, GAT-1 and GAT-3, display different distributions in the rat hippocampus. J. Comp. Neurol. 367:595–606.PubMedGoogle Scholar
  57. 57.
    Ribak, C. E., Tong, W. M., and Brecha, N. C. 1996. Astrocytic processes compensate for the apparent lack of GABA transporters in the axon terminals of cerebellar Purkinje cells. Anat. Embryol. 193:379–390.Google Scholar
  58. 58.
    De Biasi, S., Vitellaro-Zuccarello, L., and Brecha, N. C. 1998. Immunoreactivity for the GABA transporter-1 and GABA transporter-3 is restricted to astrocytes in the rat thalamus: a light and electron-microscopic immunolocalization. Neuroscience 83:815–828.PubMedGoogle Scholar
  59. 59.
    Borden, L. A. 1996. GABA transporter heterogeneity: pharmacology and cellular localization. Neurochem. Int. 29:335–356.PubMedGoogle Scholar
  60. 60.
    Norenberg, M. D., Vastag, M., and Zhou, B.-G. 2000. GABA Transporters in cultured rat astrocytes and neurons. J. Neurochem. 74 (Suppl.):S80.Google Scholar
  61. 61.
    Ebert, U. and Krnjevic, K. 1990. Systemic CI-966, a new gamma-aminobutyric acid uptake blocker, enhances gamma-aminobutyric acid action in CA1 pyramidal layer in situ. Can. J. Physiol. Pharmacol. 68:1194–1199.PubMedGoogle Scholar
  62. 62.
    Mitchell, S. J. and Silver, R. A. 2000. GABA spillover from single inhibitory axons suppresses low-frequency excitatory transmission at the cerebellar glomerulus. J. Neurosci. 20:8651–8658.PubMedGoogle Scholar
  63. 63.
    Rossi, D. J. and Hamann, M. 1998. Spillover-mediated transmission at inhibitory synapses promoted by high affinity α6 subunit GABAA receptors and glomerular geometry. Neuron 20:783–795.PubMedGoogle Scholar
  64. 64.
    Ichinose, T. and Lukasiewicz, P. D. 2002. GABA transporters regulate inhibition in the retina by limiting GABAC receptor activation. J. Neurosci. 22:3285–3292.PubMedGoogle Scholar
  65. 65.
    Fink-Jensen, A., Suzdak, P. D., Sweberg, M. D., Judge, M. E., Hansen, L., and Nielsen, P. G. 1992. The GABA uptake inhibitor, TGB, increases extracellular brain levels of GABA in awake rats. Eur. J. Pharmacol. 20:197–201.Google Scholar
  66. 66.
    Richards, D. A. and Bowery, N. G. 1996. Comparative effects of the GABA uptake inhibitors, tiagabine and NNC-711, on extracellular GABA levels in the rat ventrolateral thalamus. Neurochem. Res. 21:135–140.PubMedGoogle Scholar
  67. 67.
    Juhász, G., Kékesi, K. A., Nyitrai, G., Dobolyi, A., Krogsgaard-Larsen, P., and Schousboe, A. 1997. Differential effects of nipecotic acid and 4,5,6,7–tetrahydroisoxazolo[4,5–c]pyridin-3–ol on extracellular γ-aminobutyrate levels in rat thalamus. Eur. J. Pharmacol. 331:139–144.PubMedGoogle Scholar
  68. 68.
    Iversen, L. L. and Kelly, J. S. 1975. Uptake and metabolism of γ-aminobutyric acid by neurones and glial cells. Biochem. Pharmacol. 24:933–938.PubMedGoogle Scholar
  69. 69.
    Falch, E., Perregaard, J., Frølund, B., Søkilde, B., Buur, A., Hansen, L. M., Frydenvang, K., Brehm, L., Bolvig, T., Larsson, O. M., Sanchez, C., White, H. S., Schousboe, A., and Krogsgaard-Larsen, P. 1999. Selective inhibitors of glial GABA uptake: Synthesis, absolute stereochemistry and pharmacology of the enantiomers of 3–hydroxy-4–amino-4,5,6,7–tetrahydro-1, 2–benzisoxazole (Exo-THPO) and analogues. J. Med. Chem. 42:5402–5414.PubMedGoogle Scholar
  70. 70.
    White, H. S., Sarup, A., Bolvig, T., Kristensen, A. S., Petersen, G., Nelson, N., Pickering, D. S., Larsson, O. M., Frølund, B., Krogsgaard-Larsen, P., and Schousboe, A. 2002. Correlation between anticonvulsant activity and inhibitory action on glial GABA uptake of the highly selective mouse GAT1 inhibitor 3–hydroxy-4–amino-4,5,6,7–tetrahydro-1,2–benzisoxazole (exo-THPO) and its N-alkylated analogs. J. Pharmacol. Exp. Therap. 302, 636–644.Google Scholar
  71. 71.
    Meldrum, B. S. 1975. Epilepsy and γ-aminobutyric acid-mediated inhibition. Int. Rev. Neurobiol. 17:1–36.PubMedGoogle Scholar
  72. 72.
    Wood, J. D. 1975. The role of gamma-aminobutyric acid in the mechanism of seizures. Prog Neurobiol. 5:77–95.PubMedGoogle Scholar
  73. 73.
    Löscher, W. 1998. New visions in the pharmacology of anticonvulsion. Eur. J. Pharmacol. 342:1–13.PubMedGoogle Scholar
  74. 74.
    Suszdak, P. D. and Jansen, J. A. 1995. A review of the preclinical pharmacology of tiagabine: a potent and selective anticonvulsant GABA uptake inhibitor. Epilepsia 36:612–626.PubMedGoogle Scholar
  75. 75.
    Braestrup, C., Nielsen, E. B., Sonnewald, U., Knutsen, L. J. S., Andersen, K. E., Jansen, J. A., Frederiksen, K., Andersen, P. H., Mortensen, A., and Suzdak, P. D. 1990. (R)-N-[4,4–bis(3–methyl-2–thienyl)but-3–en-1–yl]nipecotic acid binds with high affinity to the brain γ-aminobutyric acid uptake carrier, J. Neurochem. 54:639–647.PubMedGoogle Scholar
  76. 76.
    Schousboe, A. 1979. Effects of GABA analogues on the high-affinity uptake of GABA in astrocytes in primary cultures. Pages 219–237, in Mandel, P. and De Feudis, F. V. (eds.), GABA: Biochemistry and CNS Function, Plenum Publishing, New York.Google Scholar
  77. 77.
    Schousboe, A., Larsson, O. M., Wood, J. D., and Krogsgaard-Larsen, P. 1983. Transport and metabolism of GABA in neurons and glia: implications for epilepsy. Epilepsia 24:531–538.PubMedGoogle Scholar
  78. 78.
    Gonsalves, S. F., Twitchell, B., Harbaugh, R. E., and Krogsgaard-Larsen, P., and Schousboe, A. 1989. Anticonvulsant activity of intracerebroventricularly administered glial GABA uptake inhibitors and other GABAmimetics in chemical seizure models. Epilepsy Res. 4:34–41.PubMedGoogle Scholar
  79. 79.
    Gonsalves, S. F., Twitchell, B., Harbaugh, R. E., Krogsgaard-Larsen, P., and Schousboe, A. 1989. Anticonvulsant activity of the glial GABA uptake inhibitor, THAO, in chemical seizures. Eur. J. Pharmacol. 168:265–268.PubMedGoogle Scholar
  80. 80.
    Corey, J. L., Davidson, N., Lester, H. A., Brecha, N., and Quick, M. W. 1994. Protein kinase C modulates the activity of a cloned γ-aminobutyric acid transporter expressed in Xenopus oocytes via regulated subcellular distribution of the transporter J. Biol. Chem. 269:14759–14767.PubMedGoogle Scholar
  81. 81.
    Gomeza, J., Gimenez, C., and Zafra, F. 1994. Cellular distribution and regulation by cAMP of the GABA transporter (GAT-1) mRNA. Molec. Brain Res. 21:150–156.PubMedGoogle Scholar
  82. 82.
    Osawa, I., Saito, N., Koga, T., and Tanaka, C. 1994. Phorbol ester-induced inhibition of GABA uptake by synaptosomes and by Xenopus oocytes expressing GABA transporter (GAT-1). Neurosci. Res. 19:287–293.PubMedGoogle Scholar
  83. 83.
    Tian, Y., Kapatos, G., Granneman, J. G., and Bannon, M. J. 1994. Dopamine and γ-aminobutyric acid transporters: Differential regulation by agents that promote phosphorylation. Neurosci. Lett. 173:143–146.PubMedGoogle Scholar
  84. 84.
    Nissen, J., Schousboe, A., Halkier, T., and Schousboe, I. 1992. Purification and characterization of an astrocyte GABA-carrier inducing protein (GABA-CIP) released from cerebellar granule cells. Glia 6:236–243.PubMedGoogle Scholar
  85. 85.
    Bernstein, E. M. and Quick, M. W. 1999. Regulation of gamma-aminobutyric acid (GABA) transporters by extracellular GABA. J. Biol. Chem. 274:889–895.PubMedGoogle Scholar
  86. 86.
    Quick, M. W. 2002. Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A-dependent manner. Proc. Natl. Acad. Sci. USA 99:5686–5691.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Arne Schousboe
    • 1
  1. 1.Department of PharmacologyThe Royal Danish School of PharmacyCopenhagenDenmark

Personalised recommendations