Measuring and Controlling the Extracellular Glycine Concentration at the NMDA Receptor Level

  • Philippe Ascher
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 268)


In 1987, Jon Johnson and I reported that glycine potentiated the NMDA responses of mouse embryonic neurones in primary cultures. This observation raised three questions:
  • Is the link between glycine and NMDA a general feature of NMDA receptors ?

  • What are the molecular mechanisms of the glycine-NMDA interaction ?

  • What is the physiological significance of the glycine-NMDA interaction?

Although important advances have been made towards answering these three questions, progress has been limited by the difficulty of measuring and of controlling the glycine concentration in the extracellular space.


NMDA Receptor Kynurenic Acid Apparent Dissociation Constant Glycine Site Glycine Concentration 
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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  1. Ascher, P., Henderson, G. and Johnson, J.W., 1988, Dual inhibitory actions of kynurenate on the N-methyl-D-aspartate (NMDA)-activated response•of cultured mouse cortical neurones. J. Physiol. (London), 406:1411.Google Scholar
  2. Birch, P.J., Grossman, C.J. and Hayes, A.G. 1988, Kynurenic acid antagonizes responses to NMDA via an action at the strychnine-insensitive glycine receptor. Eur. J. Pharmacol, 154: 85.PubMedCrossRefGoogle Scholar
  3. Bowery, N.G., 1987, Glycine binding sites and NMDA receptors in brain. Nature, 326: 338.PubMedCrossRefGoogle Scholar
  4. Bristow, D.R., Bowery, N.G. and Woodruff, G.N., 1986, Light microscopic localization of [3H] glycine and [3H] strychnine binding sites in rat brain. Eur. J. Pharmacol, 126: 303.PubMedCrossRefGoogle Scholar
  5. Cotman, C.W., Monaghan, D.T., Ottersen, O.P., and Storm-Mathisen, J., 1987, Anatomical organization of excitatory amino acid receptors and their pathways. Trends Neurosci, 10: 273.CrossRefGoogle Scholar
  6. de Feudis, F.V., Orsensanz-Munoz, L.M. and Fando, J.L., 1978, High-affinity glycine binding sites in rat CNS: regional variation and strychnine sensitivity. Gen. Pharmacol, 9: 171.CrossRefGoogle Scholar
  7. Fletcher, E.J. and Lodge, D. 1988, Glycine reverses antagonism of N-methyl-D-aspartate by 1hydroxy-3-aminopyrrolidone-2 (HA-966) but not by D-2-amino-5-phosphonovalerate (D-AP5) in rat cortical slices. Eur. J. Pharmacol, 151: 161.PubMedCrossRefGoogle Scholar
  8. Fletcher, É.J., Millar, J.D., Zeman, S. and Lodge, D. 1989, Non-competitive antagonism of Nmethyl-D-aspartate by displacement of an endogenous glycine-like substance. Eur. J. Neurosci 1: 196.PubMedCrossRefGoogle Scholar
  9. Foster, A.C. and Kemp, J.A., 1989, HA-966 antagonizes N-methyl-D-aspartate receptors through a selective interaction with the glycine modulatory site. J. Neurosci 9: 2191.PubMedGoogle Scholar
  10. Johnson J.W. and Ascher, P., 1987b, Interaction of glycine with the N-methyl-D-aspartate receptor. Soc. Neurosci. Abstr, 13: 383.Google Scholar
  11. Johnson, J.W. and Ascher, P. 1987a, Glycine potentiates the NMDA response in cultured mouse brain neurones. Nature, 325: 529.PubMedCrossRefGoogle Scholar
  12. Johnson, J.W., and Ascher, P., 1988, The NMDA receptor and its channel. Modulation by magnesium and by glycine, in: Excitatory amino acids in health and disease’, D. Lodge, ed. John Wiley, Chichester.Google Scholar
  13. Kemp, J.A., Foster, A.C., Leeson, P.D., Priestley, T., Tridgett, D., Iversen, L.L. and Woodruff, G.N. 1988, 7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex. Proc. Natl. Acad. Sci. USA, 85:6547.Google Scholar
  14. Kessler, M., Baudry, M., Terramani, T. and Lynch, G. 1987, Complex interactions between a glycine binding site and NMDA receptors. Soc. Neurosci. Abstr, 13: 760.Google Scholar
  15. Kessler, M., Terramani, T., Lynch, G. and Baudry, M., 1989, A glycine site associated with Nmethyl-D-aspartic acid receptors: characterization and identification of a new class of antagonists. J. Neurochem, 52: 1319.PubMedCrossRefGoogle Scholar
  16. Kishimoto, H., Simon, J.R., and Aprison, M.H., 1981, Determination of the equilibrium dissociation constants and number of glycine binding sites in several areas of the rat central nervous system using a sodium-independent system. J. Neurochem, 37: 1015.PubMedCrossRefGoogle Scholar
  17. Kleckner, N.W. and Dingledine, R. 1988, Requirement for glycine in activation of NMDAreceptors expressed in Xenopus oocytes. Science, 241: 835.PubMedCrossRefGoogle Scholar
  18. Larson, A.A., and Beitz, A.J., 1988, Glycine potentiates strychnine-induced convulsions: role of NMDA receptors. J. Neurosci, 8: 3822.PubMedGoogle Scholar
  19. Mayer, M.L., Vyklicky L. Jr. and Clements, J., 1989, Regulation of NMDA receptor desensitization in mouse hippocampal neurons by glycine. Nature, 338: 425.PubMedCrossRefGoogle Scholar
  20. Minota, S., Miyazaki, I., Wang, M.Y., Read, H.L., and Dun, N.J., 1989, Glycine potentiates NMDA responses in rat hippocampal CA1 neurons. Neurosci. Lett, 100: 237.PubMedCrossRefGoogle Scholar
  21. Monaghan, D.T., Olverman, H.J., Nguyen, L., Watkins, J.C., and Cotman, C.W., 1988, Two classes of N-methyl-D)aspartate recognition sites: differential distribution and differential regulation by glycine. Proc. Natl. Acad. Sci. USA, 85: 9836.PubMedCrossRefGoogle Scholar
  22. Monaghan, D.T., Lin, H.S., and Cotman, C.W., 1989, Two classes and two states of NMDA receptors, Soc. Neurosci. Abstr, 15: 199.Google Scholar
  23. Salt, T.E., 1989, Modulation of NMDA receptor-mediated responses by glycine and D-serine in the rat thalamus in vivo. Brain Res, 481: 403.CrossRefGoogle Scholar
  24. Sather, W., Johnson, J.W., Henderson, G. and Ascher, P., 1989, Desensitization of NMDA responses in outside-out patches persists in low calcium, high glycine solution. Soc. Neurosci. Abstr 15: 325.Google Scholar
  25. Thomson, A.M. 1989, Glycine modulation of the NMDA receptor-channel complex. Trends Neurosci. 12: 34.CrossRefGoogle Scholar
  26. Thomson, A.M., Walker, V.E., and Flynn, D.M., 1989, Glycine enhances NMDA- receptor mediated synaptic potentials in neocortical slices. Nature, 338: 422.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Philippe Ascher
    • 1
  1. 1.Laboratoire de NeurobiologieEcole Normale SupérieureParis Cedex 05France

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