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Science 12 August 1988:
Vol. 241. no. 4867, pp. 835 - 837
DOI: 10.1126/science.2841759
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Articles

Science, Vol 241, Issue 4867, 835-837
Copyright © 1988 by American Association for the Advancement of Science

articles

Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes

NW Kleckner and R Dingledine

Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7365.

Receptors for N-methyl-D-aspartate (NMDA) are involved in many plastic and pathological processes in the brain. Glycine has been reported to potentiate NMDA responses in neurons and in Xenopus oocytes injected with rat brain messenger RNA. Glycine is now shown to be absolutely required for activation of NMDA receptors in oocytes. In voltage-clamped oocytes, neither perfusion nor rapid pressure application of NMDA onto messenger RNA-injected oocytes caused a distinct ionic current without added glycine. When glycine was added, however, NMDA evoked large inward currents. The concentration of glycine required to produce a half-maximal response was 670 nanomolar, and the glycine dose-response curve extrapolated to zero in the absence of glycine. Several analogs of glycine could substitute for glycine, among which D-serine and D-alanine were the most effective. The observation that D-amino acids are effective will be important in developing drugs targeted at the glycine site.


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J. Biol. Chem. 273, 11158-11163
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Evidence for a Tetrameric Structure of Recombinant NMDA Receptors.
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Developmental Changes in NMDA Receptor Glycine Affinity and Ifenprodil Sensitivity Reveal Three Distinct Populations of NMDA Receptors in Individual Rat Cortical Neurons.
J. N. C. Kew, J. G. Richards, V. Mutel, and J. A. Kemp (1998)
J. Neurosci. 18, 1935-1943
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Chronic Administration of a Glycine Partial Agonist Alters the Expression of N-Methyl-D-aspartate Receptor Subunit mRNAs.
S. Bovetto, P.-A. Boyer, P. Skolnick, and L. H. Fossom (1997)
J. Pharmacol. Exp. Ther. 283, 1503-1508
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The "Kynurenate Test," a Biochemical Assay for Putative Cognition Enhancers.
A. Pittaluga, D. Vaccari, and M. Raiteri (1997)
J. Pharmacol. Exp. Ther. 283, 82-90
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Potentiation of NMDA Receptor-Mediated Responses by Dynorphin at Low Extracellular Glycine Concentrations.
L. Zhang, R. W. Peoples, M. Oz, J. Harvey-White, F. F. Weight, and U. Brauneis (1997)
J Neurophysiol 78, 582-590
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Control of NMDA Receptor Activation by a Glycine Transporter Co-Expressed in Xenopus Oocytes.
S. Supplisson and C. Bergman (1997)
J. Neurosci. 17, 4580-4590
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Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor.
S. A. Lipton, W.-K. Kim, Y.-B. Choi, S. Kumar, D. M. D'Emilia, P. V. Rayudu, D. R. Arnelle, and J. S. Stamler (1997)
PNAS 94, 5923-5928
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Partition of Transient and Sustained Inhibitory Glycinergic Input to Retinal Ganglion Cells.
Y. Han, J. Zhang, and M. M. Slaughter (1997)
J. Neurosci. 17, 3392-3400
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An Alanine Residue in the M3-M4 Linker Lines the Glycine Binding Pocket of the N-Methyl-D-aspartate Receptor.
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J. Biol. Chem. 272, 3532-3537
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Familial and developmental abnormalities of frontal lobe function and neurochemistry in schizophrenia.
J.F.W. Deakin, M.D.C. Simpson, P. Slater, and J.S.E. Hellewell (1997)
J Psychopharmacol 11, 133-142
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Heteromeric NMDA Receptors: Molecular and Functional Distinction of Subtypes.
H. Monyer, R. Sprengel, R. Schoepfer, A. Herb, M. Higuchi, H. Lomeli, N. Burnashev, B. Sakmann, and P. H. Seeburg (1992)
Science 256, 1217-1221
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Calcium as a coagonist of inositol 1,4,5-trisphosphate-induced calcium release.
E. Finch, T. Turner, and S. Goldin (1991)
Science 252, 443-446
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Permeation of calcium ions through non-NMDA glutamate channels in retinal bipolar cells.
T. Gilbertson, R Scobey, and M Wilson (1991)
Science 251, 1613-1615
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Acetylcholine and GABA mediate opposing actions on neuronal chloride channels in crayfish.
C Pfeiffer-Linn and R. Glantz (1989)
Science 245, 1249-1251
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J. Huettner (1989)
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