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Amino acid neurotransmission: Dynamics of vesicular uptake

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Abstract

Glutamate, GABA and glycine, the major neurotransmitters in CNS, are taken up and stored in synaptic vesicles by a Mg2+-ATP dependent process. The main driving force for vesicular glutamate uptake is the membrane potential, whereas both the membrane potential and the proton gradient contribute to the uptake of GABA and glycine. Glutamate is taken up by a specific transporter with no affinity for aspartate. Evans blue and related dyes are competitive inhibitors of the uptake of glutamate. GABA, β-alanine, and glycine are taken up by the same family of transporter molecules. Aspartate, taurine, and proline are not taken up by any synaptic vesicle preparations. It is suggested that vesicular uptake and release are characteristics that identify these amino acids as neurotransmitters. We also discuss that “quanta” in the brain are not necessarily related the content of neurotransmitter in the synaptic vesicles, but rather to postsynaptic events.

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References

  1. Krnjevic, K. 1970. Glutamate and γ-aminobutyric acid in brain. Nature (Lond.) 228:119–124.

    Article  CAS  Google Scholar 

  2. Aprison, M. H., Shank, R. P., and Davidoff, R. A. 1969. A comparison of the concentration of glycine, a transmitter suspect, in different areas of the brain and spinal cord in seven different vertebrates. Comp. Biochem. Physiol. 28:1345–1355.

    Article  PubMed  CAS  Google Scholar 

  3. Fonnum, F. 1984. Glutamate: A neurotransmitter in mammalian brain. J. Neurochem. 42:1–11.

    Article  PubMed  CAS  Google Scholar 

  4. Fonnum, F. 1984. Biochemistry, anatomy and pharmacology of GABA neurons. Pages 173–182,in Meltzer, H. Y. (ed.) Psycopharmacology: The third generation of progress. Raven Press, New York.

    Google Scholar 

  5. Castillo, J. del, and Katz, B. 1956. Biophysical aspects of neuromuscular transmission. Prog. Biophys. Chem. 6:121–170.

    Google Scholar 

  6. Fatt, P., and Katz, B. 1952. Spontaneous subthreshold activity at motor endings. J. Physiol. (Lond.) 117:109–128.

    CAS  Google Scholar 

  7. De Robertis, E. D. P. 1964. Histophysiology of synapses and neurosecretion, Pergamon. New York.

    Google Scholar 

  8. De Robertis, E. D. P., Rodriguez de Lores Arnaiz, G., Salganicoff, L., Pellegrino de Iraldi, A., and Zieher, L. M. 1963. Isolation of synaptic vesicles and structural organization of the acetylcholine system within brain nerve endings. J. Neurochem. 10:225–235.

    Article  Google Scholar 

  9. Whittaker, V. P., Michaelson, I. A., and Kirkland, R. J. A. 1964. The separation of synaptic vesicles from nerve-ending particles (“synaptosomes”). Biochem. J. 90:293–303.

    PubMed  CAS  Google Scholar 

  10. Mangan, J. L., and Whittaker, V. P. 1966. The distribution of free amino acids in subcellular fractionations of guinea-pig brain. Biochem. J. 98:128–137.

    PubMed  CAS  Google Scholar 

  11. Fonnum, F. 1967. The compartmentation of choline acetyltransferase within the synaptosome. Biochem. J. 130:262–270.

    Google Scholar 

  12. Fonnum, F. (ed.) 1978. NATO Advanced Study Institutes Series, Serie A, Life Sciences, Vol 16: Amino Acids as Chemical Transmitters, Plenum Press, New York.

    Google Scholar 

  13. Anderson, D. C., King, S. C. and Parsons, S. M. 1983. Pharmacological characterization of acetylcholine transport system in purifiedTorpedo electric organ synaptic vesicles. Molec. Pharmacol. 24:48–54.

    CAS  Google Scholar 

  14. Paulsen, O., and Heggelund P. 1994. The quantal size at retinogeniculate synapse determined from spontaneous and evoked EPSCs in guinea-pig thalamic slices. J. Physiol. 480:505–511.

    PubMed  CAS  Google Scholar 

  15. Edwards, F. A., Konnerti, A., and Sakman B. 1990. Quantal analysis of inhibitory synaptic transmission in the dentate gyros rat hippocampal slices: a patch-clamp study. J. Physiol. 430:213–219.

    PubMed  CAS  Google Scholar 

  16. Klein, R., Lagercrantz, H., and Zimmermann, H. 1982. Neurotransmitter Vesicles. Pages 1–375, Academic Press, New York.

    Google Scholar 

  17. Disbrow, J. K., Gershten, M. J., and Ruth, J. A. 1982. Uptake ofl-[3H]glutamic acid by crude and purified synaptic vesicles from rat brain. Biochem. Biophys. Res. Commun. 108:1221–1227.

    Article  PubMed  CAS  Google Scholar 

  18. Naito, S., and Ueda, T. 1985. Characterization of glutamate uptake into synaptic vesicles. J. Neurochem. 44:99–109.

    Article  PubMed  CAS  Google Scholar 

  19. Fykse, E. M., and Fonnum, F. 1988. Uptake of γ-aminobutyric acid by a synaptic vesicle fraction isolated from rat brain. J. Neurochem. 50:1237–1242.

    Article  PubMed  CAS  Google Scholar 

  20. Fykse, E. M., Christensen, H., and Fonnum, F. 1989. Comparison of the properties of γ-aminobutyric acid andl-glutamate uptake into synaptic vesicles isolated from rat brain. J. Neurochem. 52: 946–951.

    Article  PubMed  CAS  Google Scholar 

  21. Hell, J. W., Maycox, P. R., Stadler, H., and Jahn, R. 1988. Uptake of GABA by rat brain synaptic vesicles isolated by a new procedure, EMBO J. 7:3023–3029.

    PubMed  CAS  Google Scholar 

  22. Maycox, P. R., Deckwerth, T., Hell, J. W., and Jahn, R. 1988. Glutamate uptake by brain synaptic vesicles. J. Biol. Chem. 263: 15423–15428.

    PubMed  CAS  Google Scholar 

  23. Kish, P. E., Fischer-Bovenkerk, C., and Ueda, T. 1989. Active transport of γ-aminobutyric acid and glycine into synaptic vesicles. Proc. Natl. Acad. Sci. USA 86:3877–3881.

    Article  PubMed  CAS  Google Scholar 

  24. Christensen, H., Fykse, E. M., and Fonnum, F. 1990. Uptake of glycine into synaptic vesicles isolated from rat spinal cord. J. Neurochem. 54:1142–1147.

    Article  PubMed  CAS  Google Scholar 

  25. Nelson, N. 1991. Structure and pharmacology of the proton ATPases. TIPS 12:71–75.

    PubMed  CAS  Google Scholar 

  26. Fykse, E. M., and Fonnum, F. 1991. Transport of γ-aminobutyrate andl-glutamate into synaptic vesicles: Effect of different inhibitors on the vesicular uptake of neurotransmitters and on the Mg2+-ATPase. Biochem. J. 276:363–367.

    PubMed  CAS  Google Scholar 

  27. Roseth, S., Fykse, E. M., and Fonnum, F. 1995. Uptake ofl-glutamate into rat brain synaptic vesicles: Effect of inhibitors that binds specifically to the glutamate transporter. J. Neurochem. 65: 96–103.

    Article  PubMed  CAS  Google Scholar 

  28. Maycox, P.R., Deckwert, T., and Jahn, R. 1990. Bacteriorhodopsin drives the glutamate transporter of synaptic vesicles. EMBO J. 9:1465–1469.

    PubMed  CAS  Google Scholar 

  29. Hartinger, J., and Jahn, R. 1993. An anion binding site that regulates the glutamate transporter of synaptic vesicles. J. Biol. Chem. 268:23122–23127.

    PubMed  CAS  Google Scholar 

  30. Moriyama, M., and Yamamoto, A. 1995. Vesicularl-glutamate transporter in microvesicles from bovine pineal glands. J. Biol. Chem. 270:22314–22320.

    Article  PubMed  CAS  Google Scholar 

  31. Moriyama, Y., Maeda, M., and Futai, M. 1990. Energy coupling ofl-glutamate transport and vacuolar H+-ATPase in brain synaptic vesicles. J. Biochem. 108:689–693.

    PubMed  CAS  Google Scholar 

  32. Cidon, S., and Sihra, T. 1989. Characterization of a H+-ATPase in rat brain synaptic vesicles. J. Biol. Chem. 264:8281–8288.

    PubMed  CAS  Google Scholar 

  33. Shioi, J., Naito, S., and Ueda, T. 1989. Glutamate uptake into synaptic vesicles of bovine cerebral cortex and electrical potential difference of proton across the membrane. Biochem. J. 258:499–504.

    PubMed  CAS  Google Scholar 

  34. Tabb, J. S., Kish, P. E., Van Dyke, R., and Ueda, T. 1992. Glutamate transport in synaptic vesicles. Roles of membrane potential, pH gradient, and intravesicular pH. J. Biol. Chem. 267: 15412–15418.

    PubMed  CAS  Google Scholar 

  35. Hell, J. W., Maycox, P. R., and Jahn, R. 1990. Energy dependence and functional reconstitution of the γ-aminobutyric acid carrier from synaptic vesicles. J. Biol. Chem. 265:2111–2117.

    PubMed  CAS  Google Scholar 

  36. Njus, D., Kelley, P. M., and Harnadek, G. J. 1986. Bioenergetics of secretory vesicles. Biochim. Biophys. Acta, 853:237–266.

    PubMed  CAS  Google Scholar 

  37. Fykse, E. M., and Fonnum, F. 1989. Regional distribution of γ-aminobutyrate andl-glutamate uptake into synaptic vesicles isolated from rat brain. Neurosci. Lett. 99:300–304.

    Article  PubMed  CAS  Google Scholar 

  38. Christensen, H., Fykse, E. M., and Fonnum, F. 1991. Inhibition of γ-aminobutyrate and glycine uptake into synaptic vesicles. Eur. J. Phar.-Mo. 207:73–79.

    Article  CAS  Google Scholar 

  39. Dunlop, J., Fear, A., and Griffiths, R. 1991. Glutamate uptake into synaptic vesicles—inhibition by sulphur amino acids. Neuro-Report 2:377–379.

    CAS  Google Scholar 

  40. Fykse, E. M., Iversen, E. G., and Fonnum, F. 1992. Inhibition ofl-glutamate uptake into synaptic vesicles. Neurosci. Lett. 135: 125–128.

    Article  PubMed  CAS  Google Scholar 

  41. Logan, W. J., and Snyder, S. H. 1972. High affinity uptake systems for glycine, glutamate and aspartate in synaptosomes of rat central nervous tissue. Brain Res. 42:413–431.

    Article  PubMed  CAS  Google Scholar 

  42. Winter, H. C., and Ueda, T. 1993. Glutamate uptake system in the presynaptic vesicle: Glutamic acid analogs as inhibitors and alternates substrates. Neurochem. Res. 18:79–85.

    Article  PubMed  CAS  Google Scholar 

  43. Burger, P. M., Hell, J., Mehl, E., Krasel, C., Lottspeich, F., and Jahn, R. 1991. GABA and glycine in synaptic vesicles: Storage and transport characteristics. Neuron 7:287–293.

    Article  PubMed  CAS  Google Scholar 

  44. Christensen, H., and Fonnum, F. 1991. Uptake of glycine, GABA and glutamate by synaptic vesicles isolated from different regions of rat CNS. Neurosci. Lett. 129:217–220.

    Article  PubMed  CAS  Google Scholar 

  45. Johnston, G. A. R., and Iversen, L. L. 1971. Glycine uptake in rat central nervous system slices and homogenates: Evidence for different uptake systems in spinal cord and cerebral cortex. J. Neurochem. 18:1951–1961.

    Article  PubMed  CAS  Google Scholar 

  46. Johnson, J. W. and Ascher, P. 1987. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature, 325; 529–531.

    Article  PubMed  CAS  Google Scholar 

  47. Ottersen, O. P., Storm-Mathisen, J., and Somogyi, P. 1988. Colocalization of glycine-like and GABA-like immunoreactivities in Golgi cell terminals in the rat cerebellum: A postembedding light and electromicroscopic study. Brain Res. 450:342–353.

    Article  PubMed  CAS  Google Scholar 

  48. Ottersen, O. P., Storm-Mathisen, J., and Laake, J. 1990. Cellular and subcellular localization of glycine studied by quantitative electron microscopic immunocytochemistry. Pages 303–328. in Ottersen, O. P., and Storm-Mathisen, J. (eds.) Glycine Neurotransmission. Wiley, Chichester.

    Google Scholar 

  49. Tabb, J. S., and Ueda, T. 1991. Phylogenetic studies on the synaptic vesicle glutamate transport. J. Neurosci. 11:1822–1828.

    PubMed  CAS  Google Scholar 

  50. Roseth, S., and Fonnum, F. 1995. A study of the uptake of glutamate, γ-aminobutyric acid (GABA), glycine and β-alanine in synaptic brain vesicles from fish and avians. Neurosci. Lett. 183: 62–66.

    Article  PubMed  CAS  Google Scholar 

  51. Kish, P. E., Kim, S. Y., and Ueda, T. 1989b. Ontogeny of glutamate accumulating activity in rat brain synaptic vesicles. Neurosci. Lett. 97:185–190.

    Article  PubMed  CAS  Google Scholar 

  52. Christensen, H., and Fonnum, F. 1991. The ontogeny of the uptake systems for glycine, GABA, and glutamate in synaptic vesicles isolated from rat spinal cord-medulla. Dev. Brain Res. 64:155–159.

    Article  CAS  Google Scholar 

  53. Christensen, H., and Fonnum, F. 1992. The ontogeny of the uptake systems for glutamate. GABA, and glycine in synaptic vesicles isolated from rat brain. Neurochem. Res. 17:457–462.

    Article  PubMed  CAS  Google Scholar 

  54. Roseth, S., and Fonnum, F. 1996. Glutamate uptake into synaptic vesicles. Inhibition by dyes. (submitted).

  55. Liu, Y., Peter, D., Roghani, A., Schuldiner, S., Privé, G. G., Eisenberg, D., Brecha, N., and Edwards, R. H. 1992. A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter. Cell 70:539–551.

    Article  PubMed  CAS  Google Scholar 

  56. Erickson, J. D., Eiden, L. E., and Hoffman, B. 1992. Expression cloning of a reserpine-sensitive vesicular monoamine transporter. Proc. Natl. Acad. Sci. 89:10993–10997.

    Article  PubMed  CAS  Google Scholar 

  57. Usdin, T. B., Eide, L. E., Bonner, T. I., and Erickson, J. D. 1995. Molecular biology of the vesicular ACh transporter. TINS 18:218–224.

    PubMed  CAS  Google Scholar 

  58. Aprison, M. H., and Werman, R. 1968. A combined neurochemical and neurophysiological approach to the identification of central nervous system transmitters. Neuroscience Res. 1:143–174.

    CAS  Google Scholar 

  59. Nadler, J. V., White, W. F., Vaea, K. W., Perry, B. W., and Cotman, C. W. 1978. Biochemical correlates of transmission mediated by glutamate and aspartate. J. Neurochem. 51:147–155.

    Google Scholar 

  60. Nagelhus, E. A., Lehman, A., and Ottersen, O. P. 1993. Neuronal glial exchange of taurine during hypoosmotic stress. Neurosci. 54: 615–631.

    Article  CAS  Google Scholar 

  61. Sandberg, M., and Jacobson, I. 1981. β-Alanine, a possible neurotransmitter in the visual system. J. Neurochem. 37:1353–1356.

    Article  PubMed  CAS  Google Scholar 

  62. Fonnum, F. 1991. Neurochemical studies on glutamate-mediated neurotransmission. Pages 15–25,in Meldrum, B. S., Moroni, F., Simon, R. P., and Woods, J. H. (eds.) Excitatory Amino Acids, Fidia Research Foundation Symposium Series, Vol. 5, Raven Press, New York.

    Google Scholar 

  63. Gundersen, V., Shupliakov, O., Brodin, L., Ottersen, O. P., and Storm-Mathisen, J. 1995. Quantitation of excitatory amino acid uptake at intact glutamatergic synapses by immunocytochemistry of exogenousd-aspartate. J. Neurosci. 15:4417–4428.

    PubMed  CAS  Google Scholar 

  64. Fonnum, F., Storm-Mathisen, J., and Walberg, F. 1970. Glutamate decarboxylase in inhibitory neurons. A study of the enzyme in Purkinje cell axons and boutons in the cat. Brain Res. 20:259–275.

    Article  PubMed  CAS  Google Scholar 

  65. Fonnum, F., and Walberg, F. 1973. An estimation of the concentration of γ-aminobutyric acid and glutamate decarboxylase in the inhibitory Purkinje axon terminals of the cat. Brain Res. 54:115–127.

    Article  PubMed  CAS  Google Scholar 

  66. Südhof, T. C., DeCamilli, P., Niemann, H., and Jahn, R. 1993. Membrane fusion machinery: Insights from synaptic proteins. Cell 75:1–4.

    PubMed  Google Scholar 

  67. Rosenthal, L., and Meldolesi, J. 1989. α-Latrotoxin and related toxins. Pharmac. Ther. 42:115–134.

    Article  CAS  Google Scholar 

  68. Fonnum, F. 1995. Inhibition of vesicular uptake decreases Ca2+ dependent release of amino acid transmitters. J. Neurochem. 65: S50D.

    Google Scholar 

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  1. Division for Environmental Toxicology, Norwegian Defence Research Establishment, P.O. Box 25, N-2007, Kjeller, Norway

    Else Marie Fykse & Frode Fonnum

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Special issue dedicated to Dr. Herman Bachelard.

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Fykse, E.M., Fonnum, F. Amino acid neurotransmission: Dynamics of vesicular uptake. Neurochem Res 21, 1053–1060 (1996). https://doi.org/10.1007/BF02532415

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