Skip to main content
SpringerLink
Log in

Pharmacology and electrophysiology of excitatory amino acid receptors

  • Chapter
NMDA Antagonists as Potential Analgesic Drugs

Part of the book series: Progress in Inflammation Research ((PIR))

  • 128 Accesses

Abstract

The glutamatergic system supplies a ubiquitous and powerful depolarizing excitatory input to synapses throughout the mammalian central nervous system. In order to provide the signaling versatility demanded by such a complex system, glutamatergic synapses have been empowered with amazing flexibility arising, principally, through receptor diversity but with additional refinement imposed by variations in intrinsic membrane properties and an extensive capacity for modulation of receptor function. The excitatory effects of glutamic acid on the nervous system were first demonstrated on cortical neurones over four decades ago [1] and then subsequently on spinal neurones [2]. However, it was not until the 1970s that significant interest in glutamate was rekindled by the discovery of glutamate analogues which appeared to suggest receptor heterogeneity [3]. Thus, work in a number of laboratories suggested that these ionotropic glutamate-gated cationic channels could be conveniently divided into at least two classes, named according to their preferred agonists: N-methyl-D-aspartate (NMDA) and AMPA/kainate — the latter often being collectively referred to as non-NMDA receptors. The term non-NMDA reflects the fact that there was some controversy at the time, over whether AMPA and kainate receptors represented truly distinct receptors or whether the observed differences could be attributable to differences in agonist gating [4, 5]. These early issues were difficult to resolve due to the lack of good pharmacological tools but clarification has recently been provided by advances in chemistry and from the application of cloning strategies. Though not covered in this review, a family of glutamate-activated G-protein coupled “metabotropic” receptors were discovered some 30 or so years after Hayashi’s observation [6, 7]. The purpose of this review is to compile a molecular profile of the ionotropic glutamate receptor family and to provide insight into how diversity of function has been achieved. The focus has been deliberately biased toward the NMDA receptor subtype, in keeping with the theme of subsequent chapters, but with appropriate reference to non-NMDA ionotropic glutamate receptors to emphasise key electrophysiological and pharmacological variety. Readers requiring a more complete treatise of AMPA/kainate receptors are directed to several recent review articles [8-10].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Hayashi T (1954) Effects of sodium glutamate on the nervous system. Keio J Med 3: 183–192

    Google Scholar 

  2. Curtis DR, Phyllis JW, Watkins JC (1959) Chemical excitation of spinal neurones. Nature 183: 611–612

    PubMed  CAS  Google Scholar 

  3. Curtis DR, Johnson GAR (1974) Amino acid transmitters in the mammalian central nervous system. Ergebnisse der Physiologie, Biologischen Chemie and Experimentellen Pharmakologie 69: 97–188

    CAS  Google Scholar 

  4. Jahr CE, Stevens CF (1987) Glutamate activates multiple single channel conductances in hippocampal neurons. Nature 325: 522–525

    PubMed  CAS  Google Scholar 

  5. Cull-Candy SG, Usowicz MM (1987) Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons. Nature 325: 525–528

    PubMed  CAS  Google Scholar 

  6. Sladeczek F, Pin JP, Recasens M, Bockaert J, Weiss S (1985) Glutamate stimulates inositol phosphate formation in striatal neurones. Nature 317: 717–719

    PubMed  CAS  Google Scholar 

  7. Nicoletti F, Meek JL, Iadarola MJ, Chuang DM, Roth BL, Costa E (1986) Coupling of inositol phospholipid metabolism with excitatory amino acid recognition sites in rat hippocampus. J Neurochem 46: 40–46

    PubMed  CAS  Google Scholar 

  8. Hollmann M, Heinemann S (1994) Cloned glutamate receptors. Ann Rev Neurosci 17: 31–108

    PubMed  CAS  Google Scholar 

  9. Bettler B, Mulle C (1995) Review: neurotransmitter receptors. II. AMPA and kainite receptors. Neuropharmacol 34: 123–139

    CAS  Google Scholar 

  10. Bleakman D, Lodge D (1998) Neuropharmacology of AMPA and kainate receptors. Neuropharmacol 37: 1187–1204

    CAS  Google Scholar 

  11. Hollmann M, O’Shea-Greenfield A, Rogers SW, Heinemann S (1989) Cloning by functional expression of a member of the glutamate receptor family. Nature 342: 643–648

    PubMed  CAS  Google Scholar 

  12. Boulter J, Hollmann M, O’Shea-Greenfield A, Hartley M, Deneris E, Maron C, Heinemann S (1990) Molecular cloning and functional expression of glutamate receptor subunit genes. Science 249: 1033–1037

    PubMed  CAS  Google Scholar 

  13. Keinanen K, Wisden W, Sommer B, Werner P, Herb A, Verdoorn TA, Sakmann B, Seeburg PH (1990) A family of AMPA-selective glutamate receptors. Science 249: 556–560

    PubMed  CAS  Google Scholar 

  14. Nakanishi N, Shneider NA, Axel R (1990) A family of glutamate receptor genes: evidence for the formation of heteromultimeric receptors with distinct channel properties. Neuron 5: 569–581

    PubMed  CAS  Google Scholar 

  15. Sakimura K, Bujo H, Kushiya E, Araki K, Yamazaki M, Meguro H, Warashina A, Numa S, Mishina M (1990) Functional expression from cloned cDNAs of glutamate receptor species responsive to kainate and quisqualate. FEBS Lett 272: 73–80

    PubMed  CAS  Google Scholar 

  16. Bettler B, Egebjerg J, Sharma G, Pecht G, Hermans-Borgmeyer I, Moll C, Stevens CF, Heinemann S (1992) Cloning of a putative glutamate receptor: a low affinity kainatebinding subunit. Neuron 8: 257–265

    PubMed  CAS  Google Scholar 

  17. Kiskin NI, Krishtal OA, Tsyndrenko AY, Akaike N (1986) Are sulfhydryl groups essential for function of the glutamate-operated receptor-ionophore complex? Neurosci Lett 66: 305–310

    PubMed  CAS  Google Scholar 

  18. Wong LA, Mayer ML (1993) Differential modulation by cyclothiazide and concanavalin A of desensitization at native alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-and kainate-preferring glutamate receptors. Mol Pharmacol 44: 504–510

    PubMed  CAS  Google Scholar 

  19. Partin KM, Patneau DK, Winters CA, Mayer ML, Buonanno A (1993) Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A. Neuron 11: 1069–1082

    PubMed  CAS  Google Scholar 

  20. Werner P, Voigt M, Keinanen K, Wisden W, Seeburg PH (1991) Cloning of a putative high-affinity kainate receptor expressed predominantly in hippocampal CA3 cells. Nature 351: 742–744

    PubMed  CAS  Google Scholar 

  21. Wisden W, Seeburg PH (1993) A complex mosaic of high-affinity kainate receptors in rat brain. J Neurosci 13: 3582–3598

    PubMed  CAS  Google Scholar 

  22. Sommer B, Keinanen K, Verdoorn TA, Wisden W, Burnashev N, Herb A, Kohler M, Takagi T, Sakmann B, Seeburg PH (1990) Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS. Science 249: 1580–1585

    PubMed  CAS  Google Scholar 

  23. Moriyoshi K, Masu M, Ishii T, Shigemoto R, Mizuno N, Nakanishi S (1991) Molecular cloning and characterization of the rat NMDA receptor. Nature 354: 31–37

    PubMed  CAS  Google Scholar 

  24. Yamazaki M, Mori H, Araki K, Mori KJ, Mishina M (1992) Cloning, expression and modulation of a mouse NMDA receptor subunit. FEBS Lett 300: 39–45

    PubMed  CAS  Google Scholar 

  25. Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakmann B, Seeburg PH (1992) Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 256: 1217–1221

    PubMed  CAS  Google Scholar 

  26. Ishii T, Moriyoshi K, Sugihara H, Sakurada K, Kadotani H, Yokoi M, Akazawa C, Shigemoto R, Mizuno N, Masu M (1993) Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits. J Biol Chem 268: 2836–2843

    PubMed  CAS  Google Scholar 

  27. Meguro H, Mori H, Araki K, Kushiya E, Kutsuwada T, Yamazaki M, Kumanishi T, Arakawa M, Sakimura K, Mishina M (1992) Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs. Nature 357: 70–74

    PubMed  CAS  Google Scholar 

  28. Kutsuwada T, Kashiwabuchi N, Mori H, Sakimura K, Kushiya E, Araki K, Meguro H, Masaki H, Kumanishi T, Arakawa M et al (1992) Molecular diversity of the NMDA receptor channel. Nature 358: 36–41

    PubMed  CAS  Google Scholar 

  29. Ikeda K, Nagasawa M, Mori H, Araki K, Sakimura K, Watanabe M, Inoue Y, Mishina M (1992) Cloning and expression of the epsilon 4 subunit of the NMDA receptor channel. FEBS Lett 313: 34–38

    PubMed  CAS  Google Scholar 

  30. Ciabarra AM, Sullivan JM, Gahn LG, Pecht G, Heinemann S, Sevarino KA (1995) Cloning and characterization of chi-1: a developmentally regulated member of a novel class of the ionotropic glutamate receptor family. J Neurosci 15: 6498–6508

    PubMed  CAS  Google Scholar 

  31. Sucher NJ, Akbarian S, Chi CL, Leclerc CL, Awobuluyi M, Deitcher DL, Wu MK, Yuan JP, Jones EG, Lipton SA (1995) Developmental and regional expression pattern of a novel NMDA receptor-like subunit (NMDAR-L) in the rodent brain. J Neurosci 15: 6509–6520

    PubMed  CAS  Google Scholar 

  32. Das S, Sasaki YF, Rothe T, Premkumar LS, Takasu M, Crandall JE, Dikkes P, Conner DA, Rayudu PV, Cheung W et al (1998) Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A. Nature 393: 377–381

    PubMed  CAS  Google Scholar 

  33. Sugihara H, Moriyoshi K, Ishii T, Masu M, Nakanishi S (1992) Structures and properties of seven isoforms of the NMDA receptor generated by alternative splicing. Biochem Biophys Res Commun 185: 826–832

    PubMed  CAS  Google Scholar 

  34. Durand GM, Gregor P, Zheng X, Bennett MV, Uhl GR, Zukin RS (1992) Cloning of an apparent splice variant of the rat N-methyl-D-aspartate receptor NMDAR1 with altered sensitivity to polyamines and activators of protein kinase C. Proc Natl Acad Sci USA 89: 9359–9363

    PubMed  CAS  Google Scholar 

  35. Anantharam V, Panchal RG, Wilson A, Kolchine VV, Treistman SN, Bayley H (1992) Combinatorial RNA splicing alters the surface charge on the NMDA receptor. FEBS Lett 305: 27–30

    PubMed  CAS  Google Scholar 

  36. Hollmann M, Boulter J, Maron C, Beasley L, Sullivan J, Pecht G, Heinemann S (1993) Zinc potentiates agonist-induced currents at certain splice variants of the NMDA receptor. Neuron 10: 943–954

    PubMed  CAS  Google Scholar 

  37. Zukin RS, Bennett MV (1995) Alternatively spliced isoforms of the NMDARI receptor subunit. Trends Neurosci 18: 306–313

    PubMed  CAS  Google Scholar 

  38. Daggett LP, Johnson EC, Varney MA, Lin FF, Hess SD, Deal CR, Jachec C, Lu CC, Kerner JA, Landwehrmeyer GB et al (1998) The human N-methyl-D-aspartate receptor 2C subunit: genomic analysis, distribution in human brain, and functional expression. J Neurochem 71: 1953–1968

    PubMed  CAS  Google Scholar 

  39. McBain CJ, Mayer ML (1994) N-methyl-D-aspartic acid receptor structure and function. Physiol Rev 74: 723–760

    PubMed  CAS  Google Scholar 

  40. Whiting PJ, Priestley T (1998) Molecular biology of N-methyl-D-aspartate (NMDA)type glutamate receptors. In: AJ Turner, FA Stephenson (eds): Frontiers in neurobiology 3: amino acid neurotransmission. Portland Press, London, 153–176

    Google Scholar 

  41. Tingley WG, Roche KW, Thompson AK, Huganir RL (1993) Regulation of NMDA receptor phosphorylation by alternative splicing of the C-terminal domain. Nature 364: 70–73

    PubMed  CAS  Google Scholar 

  42. Salter MW (1998) Src, N-methyl-D-aspartate (NMDA) receptors, and synaptic plasticity. Biochem Pharmacol 56: 789–798

    PubMed  CAS  Google Scholar 

  43. Hollmann M, Maron C, Heinemann S (1994) N-glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor G1uR1. Neuron 13: 1331–1343

    PubMed  CAS  Google Scholar 

  44. Roche KW, Raymond LA, Blackstone C, Huganir RL (1994) Transmembrane topology of the glutamate receptor subunit GluR6. J Biol Chem 269: 11679–11682

    PubMed  CAS  Google Scholar 

  45. Molnar E, Baude A, Richmond SA, Patel PB, Somogyi P, Mcllhinney RA (1993) Biochemical and immunocytochemical characterization of antipeptide antibodies to a cloned GluR1 glutamate receptor subunit: cellular and subcellular distribution in the rat forebrain. Neuroscience 53: 307–326

    PubMed  CAS  Google Scholar 

  46. Hirai H, Kirsch J, Laube B, Betz H, Kuhse J (1996) The glycine binding site of the N-methyl-D-aspartate receptor subunit NR1: identification of novel determinants of coagonist potentiation in the extracellular M3–M4 loop region. Proc Natl Acad Sci USA 93: 6031–6036

    PubMed  CAS  Google Scholar 

  47. Green T, Heinemann SF, Gusella JF (1998) Molecular neurobiology and genetics: investigation of neural function and dysfunction. Neuron 20: 427–444

    PubMed  CAS  Google Scholar 

  48. Wafford KA, Bain CJ, Le Bourdelles B, Whiting PJ, Kemp JA (1993) Preferential co-assembly of recombinant NMDA receptors composed of three different subunits. NeuroReport 4: 1347–1349

    PubMed  CAS  Google Scholar 

  49. Uchino S, Sakimura K, Nagahari K, Mishina M (1992) Mutations in a putative agonist binding region of the AMPA-selective glutamate receptor channel. FEBS Lett 308: 253–257

    PubMed  CAS  Google Scholar 

  50. Stern-Bach Y, Bettler B, Hartley M, Sheppard PO, O’Hara PJ, Heinemann SF (1994) Agonist selectivity of glutamate receptors is specified by two domains structurally related to bacterial amino acid-binding proteins. Neuron 13: 1345–1357

    PubMed  CAS  Google Scholar 

  51. O’Hara PJ, Sheppard PO, Thogersen H, Venezia D, Haldeman BA, McGrane V, Houamed KM, Thomsen C, Gilbert TL, Mulvihill ER (1993) The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins. Neuron 11: 41–52

    PubMed  Google Scholar 

  52. Kuusinen A, Arvola M, Keinanen K (1995) Molecular dissection of the agonist binding site of an AMPA receptor. EMBO J 14: 6327–6332

    PubMed  CAS  Google Scholar 

  53. Armstrong N, Sun Y, Chen GQ, Gouaux E (1998) Structure of a glutamate-receptor ligand-binding core in complex with kainate. Nature 395: 913–917

    PubMed  CAS  Google Scholar 

  54. Priestley T, Laughton P, Myers J, Le Bourdelles B, Kerby J, Whiting PJ (1995) Pharmacological properties of recombinant human N-methyl-D-aspartate receptors comprising NR1a/NR2A and NR1a/NR2B subunit assemblies expressed in permanently transfected mouse fibroblast cells. Mol Pharmacol 48: 841–848

    PubMed  CAS  Google Scholar 

  55. Boeckman FA, Aizenman E (1994) Stable transfection of the NR1 subunit in Chinese hamster ovary cells fails to produce a functional N-methyl-D-aspartate receptor. Neurosci Lett 173: 189–192

    PubMed  CAS  Google Scholar 

  56. Kuryatov A, Laube B, Betz H, Kuhse J (1994) Mutational analysis of the glycine-binding site of the NMDA receptor: structural similarity with bacterial amino acid-binding proteins. Neuron 12: 1291–1300

    PubMed  CAS  Google Scholar 

  57. Laurie DJ, Seeburg PH (1994) Ligand affinities at recombinant N-methyl-D-aspartate receptors depend on subunit composition. Eur J Pharmacol 268: 335–345

    PubMed  CAS  Google Scholar 

  58. Grimwood S, Le Bourdelles B, Whiting PJ (1995) Recombinant human NMDA homomeric NR1 receptors expressed in mammalian cells form a high-affinity glycine antagonist binding site. J Neurochem 64: 525–530

    PubMed  CAS  Google Scholar 

  59. Leinders-Zufall T, Rand MN, Waxman SG, Kocsis JD (1994) Differential role of two Ca2+-permeable non-NMDA glutamate channels in rat retinal ganglion cells: kainateinduced cytoplasmic and nuclear Ca2+ signals. J Neurophysiol 72: 2503–2516

    PubMed  CAS  Google Scholar 

  60. Wafford KA, Kathoria M, Bain CJ, Marshall G, Le Bourdelles B, Kemp JA, Whiting PJ (1995) Identification of amino acids in the N-methyl-D-aspartate receptor NR1 subunit that contribute to the glycine binding site. Mol Pharmacol 47: 374–380

    PubMed  CAS  Google Scholar 

  61. Wo ZG, Oswald RE (1995) Unraveling the modular design of glutamate-gated ion channels. Trends Neurosci 18: 161–168

    PubMed  CAS  Google Scholar 

  62. Laube B, Hirai H, Sturgess M, Betz H, Kuhse J (1997) Molecular determinants of agonist discrimination by NMDA receptor subunits: analysis of the glutamate binding site on the NR2B subunit. Neuron 18: 493–503

    PubMed  CAS  Google Scholar 

  63. Anson LC, Chen PE, Wyllie DJA, Colquhoun D, Schoepfer R (1998) Identification of amino acid residues of the NR2A subunit that control glutamate potency in recombinant NR1/NR2A NMDA receptors. J Neurosci 18: 581–589

    PubMed  CAS  Google Scholar 

  64. Danysz W, Fadda E, Wroblewski JT, Costa E (1989) Different modes of action of 3amino-1-hydroxy-2-pyrrolidone (HA-966) and 7-chlorokynurenic acid in the modulation of N-methyl-D-aspartate-sensitive glutamate receptors. Mol Pharmacol 36: 912–916

    PubMed  CAS  Google Scholar 

  65. Compton RP, Hood WF, Monahan JB (1990) Evidence for a functional coupling of the NMDA and glycine recognition sites in synaptic plasma membranes. Eur J Pharmacol 188: 63–70

    PubMed  CAS  Google Scholar 

  66. Benveniste M, Clements J, Vyklicky L Jr, Mayer ML (1990) A kinetic analysis of the modulation of N-methyl-D-aspartic acid receptors by glycine in mouse cultured hippocampal neurones. J Physiol (Lond) 428: 333–357

    CAS  Google Scholar 

  67. Kemp JA, Priestley T (1991) Effects of (+)-HA-966 and 7-chlorokynurenic acid on the kinetics of N-methyl-D-aspartate receptor agonist responses in rat cultured cortical neurons. Mol Pharmacol 39: 666–670

    PubMed  CAS  Google Scholar 

  68. Priestley T, Kemp JA (1994) Kinetic study of the interactions between the glutamate and glycine recognition sites on the N-methyl-D-aspartic acid receptor complex. Mol Pharmacol 46: 1191–1196

    PubMed  CAS  Google Scholar 

  69. Hunter C, Wheaton KD, Wenthold RJ (1990) Solubilization and partial purification of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid binding sites from rat brain. J Neurochem 54: 118–125

    PubMed  CAS  Google Scholar 

  70. Blackstone CD, Moss SJ, Martin LJ, Levey AI, Price DL, Huganir RL (1992) Biochemical characterization and localization of a non-N-methyl-D-aspartate glutamate receptor in rat brain. J Neurochem 58: 1118–1126

    PubMed  CAS  Google Scholar 

  71. Hunter C, Wenthold RJ (1992) Solubilization and purification of an alpha-amino-3hydroxy-5-methylisoxazole-4-propionic acid binding protein from bovine brain. J Neurochem 58: 1379–1385

    PubMed  CAS  Google Scholar 

  72. Hampson DR, Huie D, Wenthold RJ (1987) Solubilization of kainic acid binding sites from rat brain. J Neurochem 49: 1209–1215

    CAS  Google Scholar 

  73. Brose N, Gasic GP, Vetter DE, Sullivan JM, Heinemann SF (1993) Protein chemical characterization and immunocytochemical localization of the NMDA receptor subunit NMDA R1. J Biol Chem 268: 22663–22671

    PubMed  CAS  Google Scholar 

  74. Wenthold RJ, Yokotani N, Doi K, Wada K (1992) Immunochemical characterization of the non-NMDA glutamate receptor using subunit-specific antibodies. Evidence for a hetero-oligomeric structure in rat brain. J Biol Chem 267: 501–507

    PubMed  CAS  Google Scholar 

  75. Sutcliffe MJ, Wo ZG, Oswald RE (1996) Three-dimensional models of non-NMDA glutamate receptors. Biophys J 70: 1575–1589

    PubMed  CAS  Google Scholar 

  76. Ferrer-Montiel AV, Montal M (1996) Pentameric subunit stoichiometry of a neuronal glutamate receptor. Proc Natl Acad Sci USA 93: 2741–2744

    PubMed  CAS  Google Scholar 

  77. Laube B, Kuhse J, Betz H (1998) Evidence for a tetrameric structure of recombinant NMDA receptors. J Neurosci 18: 2954–2961

    PubMed  CAS  Google Scholar 

  78. Rosenmund C, Stern-Bach Y, Stevens CF (1998) The tetrameric structure of a glutamate receptor channel. Science 280: 1596–1599

    PubMed  CAS  Google Scholar 

  79. Benveniste M, Mayer ML (1991) Kinetic analysis of antagonist action at N-methyl-Daspartic acid receptors. Two binding sites each for glutamate and glycine. Biophys J 59: 560–573

    PubMed  CAS  Google Scholar 

  80. Patneau DK, Mayer ML (1990) Structure-activity relationships for amino acid transmitter candidates acting at N-methyl-D-aspartate and quisqualate receptors. J Neurosci 10: 2385–2399

    PubMed  CAS  Google Scholar 

  81. Trussell LO, Raman IM, Zhang S (1994) AMPA receptors and rapid synaptic transmission. Sem Neurosci 6: 71–79

    CAS  Google Scholar 

  82. Chittajallu R, Braithwaite SP, Clarke VRJ, Henley JM (1999) Kainate receptors: subunits, synaptic localization and function. Trends Pharmacol Sci 20: 26–35

    PubMed  CAS  Google Scholar 

  83. Lester RA, Jahr CE (1992) NMDA channel behavior depends on agonist affinity. J Neurosci 12: 635–643

    PubMed  CAS  Google Scholar 

  84. Lester RA, Clements JD, Westbrook GL, Jahr CE (1990) Channel kinetics determine the time course of NMDA receptor-mediated synaptic currents. Nature 346: 565–567

    PubMed  CAS  Google Scholar 

  85. Clements JD, Lester RA, Tong G, Jahr CE and Westbrook GL (1992) The time course of glutamate in the synaptic cleft. Science 258: 1498–1501

    PubMed  CAS  Google Scholar 

  86. Edmonds B, Colquhoun D (1992) Rapid decay of averaged single-channel NMDA receptor activations recorded at low agonist concentration. Proc R Soc Lond B Biol Sci 250: 279–286

    CAS  Google Scholar 

  87. Pan ZZ, Tong G, Jahr CE (1993) A false transmitter at excitatory synapses. Neuron 11: 85–91

    PubMed  CAS  Google Scholar 

  88. Gibb AJ, Colquhoun D (1991) Glutamate activation of a single NMDA receptor-channel produces a cluster of channel openings. Proc R Soc Lond B Biol Sci 243: 39–45

    CAS  Google Scholar 

  89. Gibb AJ, Colquhoun D (1992) Activation of N-methyl-D-aspartate receptors by L-glutamate in cells dissociated from adult rat hippocampus. J Physiol (Lond) 456: 143–179

    CAS  Google Scholar 

  90. Stern P, Behe P, Schoepfer R, Colquhoun D (1992) Single-channel conductances of NMDA receptors expressed from cloned cDNAs: comparison with native receptors. Proc R Soc Lond B Biol Sci 250: 271–277

    CAS  Google Scholar 

  91. Wyllie DJ, Behe P, Colquhoun D (1998) Single-channel activations and concentration jumps: comparison of recombinant NR1a/NR2A and NR1a/NR2D NMDA receptors. J Physiol (Lond) 510: 1–18

    CAS  Google Scholar 

  92. Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH (1994) Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12: 529–540

    PubMed  CAS  Google Scholar 

  93. Kohr G, Eckardt S, Luddens H, Monyer H, Seeburg PH (1994) NMDA receptor channels: subunit-specific potentiation by reducing agents. Neuron 12: 1031–1040

    PubMed  CAS  Google Scholar 

  94. Kornau HC, Schenker LT, Kennedy MB, Seeburg PH (1995) Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science 269: 1737–1740

    PubMed  CAS  Google Scholar 

  95. Seeburg PH (1995) The NMDA receptor channel: molecular design of a coincidence detector. Recent Prog Horm Res 50: 19–34

    PubMed  CAS  Google Scholar 

  96. Jahr CE (1994) NMDA receptor kinetics and synaptic function. Sem Neurosci 6: 81–86

    CAS  Google Scholar 

  97. Vicini S, Wang JF, Li JH, Zhu WJ, Wang YH, Luo JH, Wolfe BB, Grayson DR (1998) Functional and pharmacological differences between recombinant N-methyl-D-aspartate receptors. J Neurophysiol 79: 555–566

    PubMed  CAS  Google Scholar 

  98. Watanabe M, Inoue Y, Sakimura K, Mishina M (1992) Developmental changes in distribution of NMDA receptor channel subunit mRNAs. NeuroReport 3: 1138–1140

    PubMed  CAS  Google Scholar 

  99. Akazawa C, Shigemoto R, Bessho Y, Nakanishi S, Mizuno N (1994) Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats. J Comp Neurol 347: 150–160

    PubMed  CAS  Google Scholar 

  100. Hestrin S (1992) Developmental regulation of NMDA receptor-mediated synaptic currents at a central synapse. Nature 357: 686–689

    PubMed  CAS  Google Scholar 

  101. Carmignoto G, Vicini S (1992) Activity-dependent decrease in NMDA receptor responses during development of the visual cortex. Science 258: 1007–1011

    PubMed  CAS  Google Scholar 

  102. Priestley T, Woodruff GN and Kemp JA (1989) Antagonism of responses to excitatory amino acids on rat cortical neurones by the spider toxin, argiotoxin636. Br J Pharmacol 97: 1315–1323

    PubMed  CAS  Google Scholar 

  103. Huettner JE (1990) Glutamate receptor channels in rat DRG neurons: activation by kainate and quisqualate and blockade of desensitization by Con A. Neuron 5: 255–266

    PubMed  CAS  Google Scholar 

  104. Lerma J, Paternain AV, Naranjo JR, Mellstrom B (1993) Functional kainate-selective glutamate receptors in cultured hippocampal neurons. Proc Nat! Acad Sci USA 90: 11688–11692

    PubMed  CAS  Google Scholar 

  105. Paternain AV, Rodriguez-Moreno A, Villarroel A, Lerma J (1998) Activation and desensitization properties of native and recombinant kainate receptors. Neuropharmacol 37: 1249–1259

    CAS  Google Scholar 

  106. Partin KM, Fleck MW, Mayer ML (1996) AMPA receptor flip/flop mutants affecting deactivation, desensitization, and modulation by cyclothiazide, aniracetam, and thiocyanate. J Neurosci 16: 6634–6647

    PubMed  CAS  Google Scholar 

  107. Jones KA, Wilding TJ, Huettner JE, Costa AM (1997) Desensitization of kainate receptors by kainate, glutamate and diastereomers of 4-methylglutamate. Neuropharmacol 36: 853–863

    CAS  Google Scholar 

  108. Wilding TJ, Huettner JE (1997) Activation and desensitization of hippocampal kainate receptors. J Neurosci 17: 2713–2721

    PubMed  CAS  Google Scholar 

  109. Wong LA, Mayer ML, Jane DE, Watkins JC (1994) Willardiines differentiate agonist binding sites for kainate-versus AMPA-preferring glutamate receptors in DRG and hippocampal neurons. J Neurosci 14: 3881–3897

    PubMed  CAS  Google Scholar 

  110. Mayer ML, Vyklicky L Jr, Clements J (1989) Regulation of NMDA receptor desensitization in mouse hippocampal neurons by glycine. Nature 338: 425–427

    PubMed  CAS  Google Scholar 

  111. Vyklicky L, Jr, Benveniste M, Mayer ML (1990) Modulation of N-methyl-D-aspartic acid receptor desensitization by glycine in mouse cultured hippocampal neurones. J Physiol (Lond) 428: 313–331

    CAS  Google Scholar 

  112. Lerma J (1992) Spermine regulates N-methyl-D-aspartate receptor desensitization. Neuron 8: 343–352

    PubMed  CAS  Google Scholar 

  113. Medina I, Filippova N, Charton G, Rougeole S, Ben-Ari Y, Khrestchatisky M, Bregestovski P (1995) Calcium-dependent inactivation of heteromeric NMDA receptor-channels expressed in human embryonic kidney cells. J Physiol (Lond) 482: 567–573

    CAS  Google Scholar 

  114. Krupp JJ, Vissel B, Heinemann SF, Westbrook GL (1998) N-terminal domains in the NR2 subunit control desensitization of NMDA receptors. Neuron 20: 317–327

    PubMed  CAS  Google Scholar 

  115. Villarroel A, Regalado MP, Lerma J (1998) Glycine-independent NMDA receptor desensitization: localization of structural determinants. Neuron 20: 329–339

    PubMed  CAS  Google Scholar 

  116. Legendre P, Rosenmund C, Westbrook GL (1993) Inactivation of NMDA channels in cultured hippocampal neurons by intracellular calcium. J Neurosci 13: 674–684

    PubMed  CAS  Google Scholar 

  117. Vyklicky L, Jr (1993) Calcium-mediated modulation of N-methyl-D-aspartate (NMDA) responses in cultured rat hippocampal neurones. J Physiol (Lond) 470: 575–600

    CAS  Google Scholar 

  118. Medina I, Filippova N, Barbin G, Ben-Ari Y, Bregestovski P (1994) Kainate-induced inactivation of NMDA currents via an elevation of intracellular Ca2+ in hippocampal neurons. J Neurophysiol 72: 456–465

    PubMed  CAS  Google Scholar 

  119. Kyrozis A, Goldstein PA, Heath MJ, MacDermott AB (1995) Calcium entry through a subpopulation of AMPA receptors desensitized neighbouring NMDA receptors in rat dorsal horn neurons. J Physiol (Lond) 485: 373–381

    CAS  Google Scholar 

  120. Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A (1984) Magnesium gates glutamate-activated channels in mouse central neurones. Nature 307: 462–465

    PubMed  CAS  Google Scholar 

  121. Cull-Candy SG, Usowicz MM (1989) Whole-cell current noise produced by excitatory and inhibitory amino acids in large cerebellar neurones of the rat. J Physiol (Lond) 415: 533–553

    CAS  Google Scholar 

  122. Ascher P, Nowak L (1988) The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurones in culture. J Physiol (Lond) 399: 247–266

    CAS  Google Scholar 

  123. Howe JR, Cull-Candy SG, Colquhoun D (1991) Currents through single glutamate receptor channels in outside-out patches from rat cerebellar granule cells. J Physiol (Lond) 432: 143–202

    CAS  Google Scholar 

  124. Cull-Candy SG (1987) Patch-clamp recording from single glutamate-receptor channels. Trends Pharmacol Sci 8: 218–224

    CAS  Google Scholar 

  125. Cull-Candy SG, Brickley SG, Misra C, Feldmeyer D, Momiyama A, Farrant M (1998) NMDA receptor diversity in the cerebellum: identification of subunits contributing to functional receptors. Neuropharmacol 37: 1369–1380

    CAS  Google Scholar 

  126. Priestley T, Ochu E, Kemp JA (1994) Subtypes of NMDA receptor in neurones cultured from rat brain. NeuroReport 5: 1763–1765

    PubMed  CAS  Google Scholar 

  127. Wyllie DJ, Behe P, Nassar M, Schoepfer R, Colquhoun D (1996) Single-channel currents from recombinant NMDA NR1a/NR2D receptors expressed in Xenopus oocytes. Proc R Soc Lond B Biol Sci 263: 1079–1086

    CAS  Google Scholar 

  128. Brimecombe JC, Boeckman FA, Aizenman E (1997) Functional consequences of NR2 subunit composition in single recombinant N-methyl-D-aspartate receptors. Proc Nall Acad Sci USA 94: 11019–11024

    CAS  Google Scholar 

  129. Cull-Candy SG, Howe JR, Ogden DC (1988) Noise and single channels activated by excitatory amino acids in rat cerebellar granule neurones. J Physiol (Lond) 400: 189–222

    CAS  Google Scholar 

  130. Wyllie DJ, Traynelis SF, Cull-Candy SG (1993) Evidence for more than one type of nonNMDA receptor in outside-out patches from cerebellar granule cells of the rat. J Physiol (Lond) 463: 193–226

    CAS  Google Scholar 

  131. Angulo MC, Lambolez B, Audinat E, Hestrin S, Rossier J (1997) Subunit composition, kinetic, and permeation properties of AMPA receptors in single neocortical nonpyramidal cells. J Neurosci 17: 6685–6696

    PubMed  CAS  Google Scholar 

  132. Swanson GT, Kamboj SK, Cull-Candy SG (1997) Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition. J Neurosci 17: 58–69

    PubMed  CAS  Google Scholar 

  133. Burnashev N, Villarroel A, Sakmann B (1996) Dimensions and ion selectivity of recombinant AMPA and kainate receptor channels and their dependence on Q/R site residues. J Physiol (Lond) 496: 165–173

    CAS  Google Scholar 

  134. Nowak LM, Wright JM (1992) Slow voltage-dependent changes in channel open-state probability underlie hysteresis of NMDA responses in Mg2+-free solutions. Neuron 8: 181–187

    PubMed  CAS  Google Scholar 

  135. MacDermott AB, Mayer ML, Westbrook GL, Smith SJ, Barker JL (1986) NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones. Nature 321: 519–522

    PubMed  CAS  Google Scholar 

  136. Mayer ML, Westbrook GL (1987) Permeation and block of N-methyl-D-aspartic acid receptor channels by divalent cations in mouse cultured central neurones. J Physiol (Lond) 394: 501–527

    CAS  Google Scholar 

  137. Iino M, Ozawa S, Tsuzuki K (1990) Permeation of calcium through excitatory amino acid receptor channels in cultured rat hippocampal neurones. J Physiol (Lond) 424: 151–165

    CAS  Google Scholar 

  138. Jahr CE, Stevens CF (1993) Calcium permeability of the N-methyl-D-aspartate receptor channel in hippocampal neurons in culture. Proc Natl Acad Sci USA 90: 11573–11577

    PubMed  CAS  Google Scholar 

  139. Mori H, Mishina M (1995) Structure and function of the NMDA receptor channel. Neuro pharmacol 34: 1219–1237

    CAS  Google Scholar 

  140. Saitoe M, Tanaka S, Takata K, Kidokoro Y (1997) Neural activity affects distribution of glutamate receptors during neuromuscular junction formation in Drosophila embryos. Dey Biol 184: 48–60

    CAS  Google Scholar 

  141. Burnashev N, Schoepfer R, Monyer H, Ruppersberg JP, Gunther W, Seeburg PH, Sakmann B (1992) Control by asparagine residues of calcium permeability and magnesium blockade in the NMDA receptor. Science 257: 1415–1419

    PubMed  CAS  Google Scholar 

  142. Mori H, Masaki H, Yamakura T, Mishina M (1992) Identification by mutagenesis of a Mg(2+)-block site of the NMDA receptor channel. Nature 358: 673–675

    PubMed  CAS  Google Scholar 

  143. Sakurada K, Masu M, Nakanishi S (1993) Alteration of Ca2+ permeability and sensitivity to Mg2+ and channel blockers by a single amino acid substitution in the N-methyl-D-aspartate receptor. J Biol Chem 268: 410–415

    PubMed  CAS  Google Scholar 

  144. Wollmuth LP, Kuner T, Seeburg PH, Sakmann B (1996) Differential contribution of the NR1-and NR2A-subunits to the selectivity filter of recombinant NMDA receptor channels. J Physiol (Lond) 491: 779–797

    CAS  Google Scholar 

  145. Akabas MH, Stauffer DA, Xu M, Karlin A (1992) Acetylcholine receptor channel structure probed in cysteine-substitution mutants. Science 258: 307–310

    PubMed  CAS  Google Scholar 

  146. Akabas MH, Kaufmann C, Archdeacon P, Karlin A (1994) Identification of acetylcholine receptor channel-lining residues in the entire M2 segment of the alpha subunit. Neuron 13: 919–27

    PubMed  CAS  Google Scholar 

  147. Kuner T, Wollmuth LP, Karlin A, Seeburg PH, Sakmann B (1996) Structure of the NMDA receptor channel M2 segment inferred from the accessibility of substituted cysteines. Neuron 17: 343–352

    PubMed  CAS  Google Scholar 

  148. Kupper J, Ascher P, Neyton J (1996) Probing the pore region of recombinant N-methylD-aspartate channels using external and internal magnesium block. Proc Natl Acad Sci USA 93: 8648–8653

    PubMed  CAS  Google Scholar 

  149. Hollmann M, Hartley M, Heinemann S (1991) Ca2+ permeability of KA-AMPA-gated glutamate receptor channels depends on subunit composition. Science 252: 851–853

    PubMed  CAS  Google Scholar 

  150. Keller BU, Hollmann M, Heinemann S, Konnerth A (1992) Calcium influx through subunits GIuR1/G1uR3 of kainate/AMPA receptor channels is regulated by cAMP dependent protein kinase. EMBO J 11: 891–896

    PubMed  CAS  Google Scholar 

  151. Verdoorn TA, Burnashev N, Monyer H, Seeburg PH, Sakmann B (1991) Structural determinants of ion flow through recombinant glutamate receptor channels. Science 252: 1715–1718

    PubMed  CAS  Google Scholar 

  152. Bowie D, Mayer ML (1995) Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block. Neuron 15: 453–462

    PubMed  CAS  Google Scholar 

  153. Donevan SD, Rogawski MA (1995) Intracellular polyamines mediate inward rectification of Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Proc Natl Acad Sci USA 92: 9298–9302

    PubMed  CAS  Google Scholar 

  154. Isa T, Iino M, Itazawa S, Ozawa S (1995) Spermine mediates inward rectification of Ca2+-permeable AMPA receptor channels. NeuroReport 6: 2045–2048

    PubMed  CAS  Google Scholar 

  155. Koh DS, Geiger JR, Jonas P, Sakmann B (1995) Ca2+-permeable AMPA and NMDA receptor channels in basket cells of rat hippocampal dentate gyrus. J Physiol (Lond) 485: 383–402

    CAS  Google Scholar 

  156. Cu C, Bahring R, Mayer ML (1998) The role of hydrophobic interactions in binding of polyamines to non NMDA receptor ion channels. Neuropharmacol 37: 1381–1391

    CAS  Google Scholar 

  157. Sommer B, Kohler M, Sprengel R, Seeburg PH (1991) RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell 67: 11–19

    PubMed  CAS  Google Scholar 

  158. Egebjerg J, Heinemann SF (1993) Ca2+ permeability of unedited and edited versions of the kainate selective glutamate receptor G1uR6. Proc Natl Acad Sci USA 90: 755–759

    PubMed  CAS  Google Scholar 

  159. Kamboj SK, Swanson GT, Cull-Candy SG (1995) Intracellular spermine confers rectification on rat calcium-permeable AMPA and kainate receptors. J Physiol (Loud) 486: 297–303

    CAS  Google Scholar 

  160. Brorson JR, Bleakman D, Chard PS, Miller RJ (1992) Calcium directly permeates kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in cultured cerebellar Purkinje neurons. Mol Pharmacol 41: 603–608

    PubMed  CAS  Google Scholar 

  161. Savidge JR, Bleakman D, Bristow DR (1997) Identification of kainate receptor-mediated intracellular calcium increases in cultured rat cerebellar granule cells. J Neurochem 69: 1763–1766

    PubMed  CAS  Google Scholar 

  162. Bettler B, Boulter J, Hermans-Borgmeyer I, O’Shea-Greenfield A, Deneris ES, Moll C, Borgmeyer U, Hollmann M, Heinemann S (1990) Cloning of a novel glutamate receptor subunit, G1uR5: expression in the nervous system during development. Neuron 5: 583–595

    PubMed  CAS  Google Scholar 

  163. Bleakman D, Schoepp DD, Ballyk B, Bufton H, Sharpe EF, Thomas K, Ornstein PL, Kamboj RK (1996) Pharmacological discrimination of GIuRS and GluR6 kainate receptor subtypes by (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahyd roisdoquinoline-3 carboxylic-acid. Mol Pharmacol 49: 581–585

    PubMed  CAS  Google Scholar 

  164. Clarke VR, Ballyk BA, Hoo KH, Mandelzys A, Pellizzari A, Bath CP, Thomas J, Sharpe EF, Davies CH, Ornstein PL et al (1997) A hippocampal G1uR5 kainate receptor regulating inhibitory synaptic transmission. Nature 389: 599–603

    PubMed  CAS  Google Scholar 

  165. Watkins JC (1962) The synthesis of some acidic amino acids possessing neuropharmacological activity. J Med Pharm Chem 5: 1187–1199

    CAS  Google Scholar 

  166. Olverman HJ, Jones AW, Watkins JC (1988) [3H]D-2-amino-5-phosphonopentanoate as a ligand for N-methyl-D-aspartate receptors in the mammalian central nervous system. Neuroscience 26: 1–15

    PubMed  CAS  Google Scholar 

  167. Watkins JC, Olverman HJ (1987) Agonists and Antagonists for Excitatory Amino Acid Receptors. Trends Pharmacol Sci 10: 265–272

    CAS  Google Scholar 

  168. Fagg GE, Olpe HR, Pozza MF, Baud J, Steinmann M, Schmutz M, Portet C, Baumann P, Thedinga K, Bittiger H (1990) CGP 37849 and CGP 39551: novel and potent competitive N-methyl-D-aspartate receptor antagonists with oral activity. Br J Pharmacol 99: 791–797

    PubMed  CAS  Google Scholar 

  169. Lowe DA, Neijt HC, Aebischer B (1990) D-CPP-ene (SDZ EAA 494), a potent and competitive N-methyl-D-aspartate (NMDA) antagonist: effect on spontaneous activity and NMDA-induced depolarizations in the rat neocortical slice preparation, compared with other CPP derivatives and MK-801. Neurosci Lett 113: 315–321

    PubMed  CAS  Google Scholar 

  170. Ornstein PL, Monn JA, Schoepp DD (1994) Antagonists of the NMDA receptor complex. DN&P 7: 5–12

    Google Scholar 

  171. Buller AL, Larson HC, Schneider BE, Beaton JA, Morrisett RA, Monaghan DT (1994) The molecular basis of NMDA receptor subtypes: native receptor diversity is predicted by subunit composition. J Neurosci 14: 5471–5484

    PubMed  CAS  Google Scholar 

  172. Leeson PD, Iversen LL (1994) The glycine site on the NMDA receptor: structure-activity relationships and therapeutic potential. J Med Chem 37: 4053–4067

    PubMed  CAS  Google Scholar 

  173. Kulagowski JJ, Leeson PD (1995) Glycine-site NMDA receptor antagonists. Exp Opin Ther Patents 5: 1061–1075

    CAS  Google Scholar 

  174. McBain CJ, Kleckner NW, Wyrick S, Dingledine R (1989) Structural requirements for activation of the glycine coagonist site of N-methyl-D-aspartate receptors expressed in Xenopus oocytes. Mol Pharmacol 36: 556–565

    PubMed  CAS  Google Scholar 

  175. Pundt LL, Narang N, Kondoh T, Low WC (1997) Localization of dopamine receptors and associated mRNA in transplants of human fetal striatal tissue in rodents with experimental Huntington’s disease. Neurosci Res 27: 305–315

    PubMed  CAS  Google Scholar 

  176. Birch PJ, Grossman CJ, Hayes AG (1988) Kynurenic acid antagonises responses to NMDA via an action at the strychnine-insensitive glycine receptor. Eur J Pharmacol 154: 85–87

    PubMed  CAS  Google Scholar 

  177. Henderson G, Johnson JW, Ascher P (1990) Competitive antagonists and partial agonists at the glycine modulatory site of the mouse N-methyl-D-aspartate receptor. J Physiol (Lond) 430: 189–212

    CAS  Google Scholar 

  178. Nagata R, Tanno N, Kodo T, Ae N, Yamaguchi H, Nishimura T, Antoku F, Tatsuno T, Kato T, Tanaka Y (1994) Tricyclic quinoxalinediones: 5, 6-dihydro-1H-pyrrolo[1,2,3de] quinoxaline-2,3-diones and 6,7-dihydro-1H,5H-pyrido[1,2,3-de] quinoxaline-2,3diones as potent antagonists for the glycine binding site of the NMDA receptor. J Med Chem 37: 3956–3968

    PubMed  CAS  Google Scholar 

  179. Nagata R, Ae N, Tanno N (1995) Structure-activity relationships of tricyclic quinoxalinediones as potent antagonists for the glycine binding site of the NMDA receptor. Bioorg Chem Lett 5: 1527–1532

    CAS  Google Scholar 

  180. Kemp JA, Foster AC, Leeson PD, Priestley T, Tridgett R, Iversen LL, Woodruff GN (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: 6547–6550

    PubMed  CAS  Google Scholar 

  181. Danysz W, Fadda E, Wroblewski JT, Costa E (1989) Kynurenate and 2-amino-5-phosphonovalerate interact with multiple binding sites of the N-methyl-D-aspartate-sensitive glutamate receptor domain. Neurosci Lett 96: 340–344

    PubMed  CAS  Google Scholar 

  182. Leeson PD, Carling RW, Moore KW, Moseley AM, Smith JD, Stevenson G, Chan T, Baker R, Foster AC, Grimwood S (1992) 4-Amido-2-carboxytetrahydroquinolines. Structure-activity relationships for antagonism at the glycine site of the NMDA receptor. J Med Chem 35: 1954–1968

    PubMed  CAS  Google Scholar 

  183. Grimwood S, Moseley AM, Carling RW, Leeson PD, Foster AC (1992) Characterization of the binding of [3H]L-689, 560, an antagonist for the glycine site on the N-methyl-Daspartate receptor, to rat brain membranes. Mol Pharmacol 41: 923–930

    PubMed  CAS  Google Scholar 

  184. Kulagowski JJ, Baker R, Curtis NR, Leeson PD, Mawer IM, Moseley AM, Ridgill MP, Rowley M, Stansfield I, Foster AC (1994) 3’-(Arylmethyl)-and 3’-(aryloxy)-3-phenyl-4hydroxyquinolin-2(1H)-ones: orally active antagonists of the glycine site on the NMDA receptor. J Med Chem 37: 1402–1405

    CAS  Google Scholar 

  185. Grimwood S, Kulagowski JJ, Mawer IM, Rowley M, Leeson PD, Foster AC (1995) Allosteric modulation of the glutamate site on the NMDA receptor by four novel glycine site antagonists. Eur J Pharmacol 290: 221–226

    CAS  Google Scholar 

  186. Woodward RM, Huettner JE, Guastella J, Keana JF, Weber E (1995) In vitro pharmacology of ACEA-1021 and ACEA-1031: systemically active quinoxalinediones with high affinity and selectivity for N-methyl-D-aspartate receptor glycine sites. Mol Pharmacol 47: 568–581

    CAS  Google Scholar 

  187. Ibuki T, Dunbar SA, Yaksh TL (1997) Effect of transient naloxone antagonism on tolerance development in rats receiving continuous spinal morphine infusion. Pain 70: 125–132

    PubMed  CAS  Google Scholar 

  188. Baron BM, Siegel BW, Harrison BL, Gross RS, Hawes C, Towers P (1996) [3H]MDL 105,519, a high-affinity radioligand for the N-methyl-D-aspartate receptor-associated glycine recognition site. J Pharmacol Exp Ther 279: 62–68

    PubMed  CAS  Google Scholar 

  189. Davies JA (1997) Remacemide hydrochloride: a novel antiepileptic agent. Gen Pharmacol 28: 499–502

    PubMed  CAS  Google Scholar 

  190. Baron BM, Harrison BL, Kehne JH, Schmidt CJ, van Giersbergen PL, White HS, Siegel BW, Senyah Y, McCloskey TC, Fadayel GM et al (1997) Pharmacological characterization of MDL 105,519, an NMDA receptor glycine site antagonist. Eur J Pharmacol 323: 181–192

    CAS  Google Scholar 

  191. Honer M, Benke D, Laube B, Kuhse J, Heckendorn R, Allgeier H, Angst C, Monyer H, Seeburg PH, Betz H et al (1998) Differentiation of glycine antagonist sites of N-methylD-aspartate receptor subtypes. Preferential interaction of CGP 61594 with NR1/2B receptors. J Biol Chem 273: 11158–11163

    PubMed  CAS  Google Scholar 

  192. Monahan JB, Biesterfeldt JP, Hood WF, Compton RP, Cordi AA, Vazquez MI, Lanthorn TH, Wood PL (1990) Differential modulation of the associated glycine recognition site by competitive N-methyl-D-aspartate receptor antagonists. Mol Pharmacol 37: 780–784

    PubMed  CAS  Google Scholar 

  193. Hood WF, Compton RP, Monahan JB (1990) N-methyl-D-aspartate recognition site ligands modulate activity at the coupled glycine recognition site. J Neurochem 54: 1040–1046

    PubMed  CAS  Google Scholar 

  194. Grimwood S, Wilde GJ, Foster AC (1993) Interactions between the glutamate and glycine recognition sites of the N-methyl-D-aspartate receptor from rat brain, as revealed from radioligand binding studies. J Neurochem 60: 1729–1738

    PubMed  CAS  Google Scholar 

  195. Fletcher EJ, Martin D, Aram JA, Lodge D, Honore T (1988) Quinoxalinediones selectively block quisqualate and kainate receptors and synaptic events in rat neocortex and hippocampus and frog spinal cord in vitro. Br J Pharmacol 95: 585–597

    CAS  Google Scholar 

  196. Honore T, Davies SN, Dreier J, Fletcher EJ, Jacobsen P, Lodge D, Nielsen FE (1988) Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists. Science 241: 701–703

    PubMed  CAS  Google Scholar 

  197. Sheardown MJ, Nielsen EO, Hansen AJ, Jacobsen P, Honore T (1990) 2, 3-Dihydroxy6-nitro-7-sulfamoyl-benzo(F)quinoxaline: a neuroprotectant for cerebral ischemia. Science 247: 571–574

    PubMed  CAS  Google Scholar 

  198. Lester RA, Quarum ML, Parker JD, Weber E, Jahr CE (1989) Interaction of 6-cyano-7nitroquinoxaline-2,3-dione with the N-methyl-D-aspartate receptor-associated glycine binding site. Mol Pharmacol 35: 565–570

    PubMed  CAS  Google Scholar 

  199. Kleckner NW, Dingledine R (1989) Selectivity of quinoxalines and kynurenines as antagonists of the glycine site on N-methyl-D-aspartate receptors. Mol Pharmacol 36: 430–436

    PubMed  CAS  Google Scholar 

  200. Randle JC, Guet T, Bobichon C, Moreau C, Curutchet P, Lambolez B, de Carvalho LP, Cordi A, Lepagnol JM (1992) Quinoxaline derivatives: structure-activity relationships and physiological implications of inhibition of N-methyl-D-aspartate and non-Nmethyl-D-aspartate receptor-mediated currents and synaptic potentials. Mol Pharmacol 41: 337–345

    PubMed  CAS  Google Scholar 

  201. O’Neill MJ, Bond A, Ornstein PL, Ward MA, Hicks CA, Hoo K, Bleakman D, Lodge D (1998) Decahydroisoquinolines: novel competitive AMPA/kainate antagonists with neuroprotective effects in global cerebral ischaemia. Neuropharmacol 37: 1211–1222

    Google Scholar 

  202. Honore T, Drejer J (1988) In: Excitatory amino acids in health and disease, John Wiley & Sons, NY, 91–106

    Google Scholar 

  203. Monaghan DT, Bridges RJ, Cotman CW (1989) The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system. Ann Rev Pharmacol Toxicol 29: 365–402

    CAS  Google Scholar 

  204. Young AB, Fagg GE (1990) Excitatory amino acid receptors in the brain: membrane binding and receptor autoradiographic approaches. Trends Pharmacol Sci 11: 126–133

    PubMed  CAS  Google Scholar 

  205. Castillo PE, Malenka RC, Nicoll RA (1997) Kainate receptors mediate a slow postsynaptic current in hippocampal CA3 neurons. Nature 388: 182–186

    PubMed  CAS  Google Scholar 

  206. Vignes M, Collingridge GL (1997) The synaptic activation of kainate receptors. Nature 388: 179–182

    PubMed  CAS  Google Scholar 

  207. Li P, Wilding TJ, Kim SJ, Calejesan AA, Huettner JE, Zhuo M (1999) Kainate-receptormediated sensory synaptic transmission in mammalian spinal cord. Nature 397: 161–164

    PubMed  CAS  Google Scholar 

  208. Williams, K (1995) Modulation of NMDA receptors by polyamines. In: RA Casero (ed): Polyamines: regulation and molecular interaction. RG Landes Co, Austin, Texas, 129–170

    Google Scholar 

  209. Dev KK, Henley JM (1998) The regulation of AMPA receptor-binding sites. Mol Neurobiol 17: 33–58

    PubMed  CAS  Google Scholar 

  210. Ransom RW, Stec NL (1988) Cooperative modulation of [3H]MK-801 binding to the Nmethyl-D-aspartate receptor-ion channel complex by L-glutamate, glycine, and polyamines. J Neurochem 51: 830–836

    PubMed  CAS  Google Scholar 

  211. Ransom RW, Deschenes NL (1990) Polyamines regulate glycine interaction with the Nmethyl-D-aspartate receptor. Synapse 5: 294–298

    PubMed  CAS  Google Scholar 

  212. Rock DM, Macdonald RL (1992) The polyamine diaminodecane (DA-10) produces a voltage-dependent flickery block of single NMDA receptor channels. Neurosci Lett 144: 111–115

    PubMed  CAS  Google Scholar 

  213. Benveniste M, Mayer ML (1993) Multiple effects of spermine on N-methyl-D-aspartic acid receptor responses of rat cultured hippocampal neurones. J Physiol (Lond) 464: 131–163

    CAS  Google Scholar 

  214. Durand GM, Bennett MV, Zukin RS (1993) Splice variants of the N-methyl-D-aspartate receptor NR1 identify domains involved in regulation by polyamines and protein kinase C. Proc Natl Acad Sci USA 90: 6731–6735

    PubMed  CAS  Google Scholar 

  215. Zhang L, Zheng X, Paupard MC, Wang AP, Santchi L, Friedman LK, Zukin RS, Bennett MV (1994) Spermine potentiation of recombinant N-methyl-D-aspartate receptors is affected by subunit composition. Proc Natl Acad Sci USA 91: 10883–10887

    PubMed  CAS  Google Scholar 

  216. Zheng X, Zhang L, Durand GM, Bennett MV, Zukin RS (1994) Mutagenesis rescues spermine and Zn’ potentiation of recombinant NMDA receptors. Neuron 12: 811–818

    PubMed  CAS  Google Scholar 

  217. Williams K, Zappia AM, Pritchett DB, Shen YM, Molinoff PB (1994) Sensitivity of the N-methyl-D-aspartate receptor to polyamines is controlled by NR2 subunits. Mol Pharmacol 45: 803–809

    PubMed  CAS  Google Scholar 

  218. Williams K (1995) Pharmacological properties of recombinant N-methyl-D-aspartate (NMDA) receptors containing the epsilon 4 (NR2D) subunit. Neurosci Lett 184: 181–184

    PubMed  CAS  Google Scholar 

  219. Reynolds IJ, Miller RJ (1989) Ifenprodil is a novel type of N-methyl-D-aspartate receptor antagonist: interaction with polyamines. Mol Pharmacol 36: 758–765

    PubMed  CAS  Google Scholar 

  220. Carter CJ, Lloyd KG, Zivkovic B, Scatton B (1990) Ifenprodil and SL 82.0715 as cerebral antiischemic agents. III. Evidence for antagonistic effects at the polyamine modulatory site within the N-methyl-D-aspartate receptor complex. J Pharmacol Exp Ther 253: 475–482

    PubMed  CAS  Google Scholar 

  221. Schoemaker H, Allen J, Langer SZ (1990) Binding of [3H]ifenprodil, a novel NMDA antagonist, to a polyamine-sensitive site in the rat cerebral cortex. Eur J Pharmacol 176: 249–250

    PubMed  CAS  Google Scholar 

  222. Williams K (1993) Ifenprodil discriminates subtypes of the N-methyl-D-aspartate receptor: selectivity and mechanisms at recombinant heteromeric receptors. Mol Pharmacol 44: 851–859

    PubMed  CAS  Google Scholar 

  223. Williams K, Russell SL, Shen YM, Molinoff PB (1993) Developmental switch in the expression of NMDA receptors occurs in vivo and in vitro. Neuron 10: 267–278

    CAS  Google Scholar 

  224. Legendre P, Westbrook GL (1991) Ifenprodil blocks N-methyl-D-aspartate receptors by a two-component mechanism. Mol Pharmacol 40: 289–298

    PubMed  CAS  Google Scholar 

  225. Kew JN, Kemp JA (1998) An allosteric interaction between the NMDA receptor polyamine and ifenprodil sites in rat cultured cortical neurones. J Physiol (Lond) 512: 17–28

    CAS  Google Scholar 

  226. Gallagher MJ, Huang H, Pritchett DB, Lynch DR (1996) Interactions between ifenprodil and the NR2B subunit of the N-methyl-D-aspartate receptor. J Biol Chem 271: 9603–9611

    PubMed  CAS  Google Scholar 

  227. Williams K, Kashiwagi K, Fukuchi J, Igarashi K (1995) An acidic amino acid in the Nmethyl-D-aspartate receptor that is important for spermine stimulation. Mol Pharmacol 48: 1087–1098

    CAS  Google Scholar 

  228. Kashiwagi K, Fukuchi J, Chao J, Igarashi K, Williams K (1996) An aspartate residue in the extracellular loop of the N-methyl-D-aspartate receptor controls sensitivity to spermine and protons. Mol Pharmacol 49: 1131–1141

    PubMed  CAS  Google Scholar 

  229. Kew JN, Richards JG, Mutel V, Kemp JA (1998) Developmental changes in NMDA receptor glycine affinity and ifenprodil sensitivity reveal three distinct populations of NMDA receptors in individual rat cortical neurons. J Neurosci 18: 1935–1943

    PubMed  CAS  Google Scholar 

  230. Fischer G, Mutel V, Trube G, Malherbe P, Kew JN, Mohacsi E, Heitz MP, Kemp JA (1997) Ro 25–6981, a highly potent and selective blocker of N-methyl-D-aspartate receptors containing the NR2B subunit. Characterization in vitro. J Pharmacol Exp Ther 283: 1285–1292

    CAS  Google Scholar 

  231. Kew JN, Trube G, Kemp JA (1998) State-dependent NMDA receptor antagonism by Ro 8–4304, a novel NR2B selective, non-competitive, voltage-independent antagonist. Br J Pharmacol 123: 463–472

    PubMed  CAS  Google Scholar 

  232. Chenard BL, Bordner J, Butler TW, Chambers LK, Collins MA, De Costa DL, Ducat MF, Dumont ML, Fox CB, Mena EE (1995) (1S, 2S)-1-(4-hydroxyphenyl)-2-(4hydroxy-4-phenylpiperidino)-1-propanol: a potent new neuroprotectant which blocks N-methyl-D-aspartate responses. J Med Chem 38: 3138–3145

    PubMed  CAS  Google Scholar 

  233. Gotti B, Duverger D, Bertin J, Carter C, Dupont R, Frost J, Gaudilliere B, MacKenzie ET, Rousseau J, Scatton B (1988) Ifenprodil and SL 82.0715 as cerebral anti-ischemic agents. I. Evidence for efficacy in models of focal cerebral ischemia. J Pharmacol Exp Ther 247: 1211–1221

    PubMed  CAS  Google Scholar 

  234. Kleinschmidt J, Zucker CL, Yazulla S (1986) Neurotoxic action of kainic acid in the isolated toad and goldfish retina: II. Mechanism of action. J Comp Neurol 254: 196–208

    PubMed  CAS  Google Scholar 

  235. Bernardi M, Bertolini A, Szczawinska K, Genedani S (1996) Blockade of the polyamine site of NMDA receptors produces antinociception and enhances the effect of morphine, in mice. Eur J Pharmacol 298: 51–55

    PubMed  CAS  Google Scholar 

  236. Sakurada T, Wako K, Sugiyama A, Sakurada C, Tan-No K, Kisara K (1998) Involvement of spinal NMDA receptors in capsaicin-induced nociception. Pharmacol Biochem Behav 59: 339–345

    PubMed  CAS  Google Scholar 

  237. Song XJ, Zhao ZQ (1998) Cooperative interaction among the various regulatory sites within the NMDA receptor-channel complex in modulating the evoked responses to noxious thermal stimuli of spinal dorsal horn neurons in the cat. Exp Brain Res 120: 257–262

    PubMed  CAS  Google Scholar 

  238. Jackson A, Sanger DJ (1988) Is the discriminative stimulus produced by phencyclidine due to an interaction with N-methyl-D-aspartate receptors? Psychopharmacol 96: 87–92

    CAS  Google Scholar 

  239. Kew JN, Trube G, Kemp JA (1996) A novel mechanism of activity-dependent NMDA receptor antagonism describes the effect of ifenprodil in rat cultured cortical neurones. J Physiol (Land) 497: 761–772

    CAS  Google Scholar 

  240. Kirson ED, Yaari Y (1996) Synaptic NMDA receptors in developing mouse hippocampal neurones: functional properties and sensitivity to ifenprodil. J Physiol (Lond) 497: 437–455

    CAS  Google Scholar 

  241. Hargreaves EL, Cain DP (1992) Hyperactivity, hyper-reactivity, and sensorimotor deficits induced by low doses of the N-methyl-D-aspartate non-competitive channel blocker MK801. Behav Brain Res 47: 23–33

    PubMed  CAS  Google Scholar 

  242. Priestley T, Marshall GR, Hill RG, Kemp JA (1998) L-687,414, a low efficacy NMDA receptor glycine site partial agonist in vitro, does not prevent hippocampal LTP in vivo at plasma levels known to be neuroprotective. Br J Pharmacol 124: 1767–1773

    PubMed  CAS  Google Scholar 

  243. Bekkers JM (1993) Enhancement by histamine of NMDA-mediated synaptic transmission in the hippocampus. Science 261: 104–106

    PubMed  CAS  Google Scholar 

  244. Vorobjev VS, Sharonova IN, Walsh IB, Haas HL (1993) Histamine potentiates Nmethyl-D-aspartate responses in acutely isolated hippocampal neurons. Neuron 11: 837–844

    PubMed  CAS  Google Scholar 

  245. Williams K (1994) Mechanisms influencing stimulatory effects of spermine at recombinant N-methyl-D-aspartate receptors. Mol Pharmacol 46: 161–168

    PubMed  CAS  Google Scholar 

  246. Traynelis SF, Hartley M, Heinemann SF (1995) Control of proton sensitivity of the NMDA receptor by RNA splicing and polyamines. Science 268: 873–876

    PubMed  CAS  Google Scholar 

  247. Igarashi K, Williams K (1995) Antagonist properties of polyamines and bis(ethyl)polyamines at N-methyl-D-aspartate receptors. J Pharmacol Exp Ther 272: 1101–1109

    PubMed  CAS  Google Scholar 

  248. Williams K (1993) Effects of Agelenopsis aperta toxins on the N-methyl-D-aspartate receptor: polyamine-like and high-affinity antagonist actions. J Pharmacol Exp Ther 266: 231–236

    PubMed  CAS  Google Scholar 

  249. Williams K (1997) Interactions of polyamines with ion channels. Biochem J 325: 289–297

    PubMed  CAS  Google Scholar 

  250. Sequeira S and Nasstrom J (1998) Low-affinity kainate receptors and long-lasting depression of NMDA-receptor-mediated currents in rat superficial dorsal horn. J Neurophysiol 80: 895–902

    PubMed  CAS  Google Scholar 

  251. Brackley PT, Bell DR, Choi SK, Nakanishi K, Usherwood PN (1993) Selective antagonism of native and cloned kainate and NMDA receptors by polyamine-containing toxins. J Pharmacol Exp Ther 266: 1573–1580

    PubMed  CAS  Google Scholar 

  252. Herlitze S, Raditsch M, Ruppersberg JP, Jahn W, Monyer H, Schoepfer R, Witzemann V (1993) Argiotoxin detects molecular differences in AMPA receptor channels. Neuron 10: 1131–1140

    PubMed  CAS  Google Scholar 

  253. Blaschke M, Keller BU, Rivosecchi R, Hollmann M, Heinemann S, Konnerth A (1993) A single amino acid determines the subunit-specific spider toxin block of alpha-amino3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor channels. Proc Natl Acad Sci USA 90: 6528–6532

    PubMed  CAS  Google Scholar 

  254. Wong EH, Kemp JA, Priestley T, Knight AR, Woodruff GN, Iversen LL (1986) The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc Natl Acad Sci USA 83: 7104–7108

    PubMed  CAS  Google Scholar 

  255. Honey CR, Miljkovic Z, MacDonald JF (1985) Ketamine and phencyclidine cause a voltage-dependent block of responses to L-aspartic acid. Neurosci Lett 61: 135–139

    PubMed  CAS  Google Scholar 

  256. Keana JF, McBurney RN, Scherz MW, Fischer JB, Hamilton PN, Smith SM, Server AC, Finkbeiner S, Stevens CF, Jahr C (1989) Synthesis and characterization of a series of diarylguanidines that are noncompetitive N-methyl-D-aspartate receptor antagonists with neuroprotective properties. Proc Natl Acad Sci USA 86: 5631–5635

    PubMed  CAS  Google Scholar 

  257. Netzer R, Pflimlin P, Trube G (1993) Dextromethorphan blocks N-methyl-D-aspartateinduced currents and voltage-operated inward currents in cultured cortical neurons. Eur J Pharmacol 238: 209–216

    PubMed  CAS  Google Scholar 

  258. Church J, Sawyer D, McLarnon JG (1994) Interactions of dextromethorphan with the N-methyl-D-aspartate receptor-channel complex: single channel recordings. Brain Res 666: 189–194

    PubMed  CAS  Google Scholar 

  259. Parsons CG, Quack G, Bresink I, Baran L, Przegalinski E, Kostowski W, Krzascik P, Hartmann S, Danysz W (1995) Comparison of the potency, kinetics and voltage-dependency of a series of uncompetitive NMDA receptor antagonists in vitro with anticonvulsive and motor impairment activity in vivo. Neuropharmacol 34: 1239–1258

    CAS  Google Scholar 

  260. Sobolevsky AI, Koshelev SG, Khodorov BI (1998) Interaction of memantine and amantadine with agonist-unbound NMDA-receptor channels in acutely isolated rat hippocampal neurons. J Physiol (Lond) 512: 47–60

    CAS  Google Scholar 

  261. Mealing GAR, Lanthorn TH, Murray CL, Small DL, Morley P (1999) Differences in degree of trapping of low-affinity uncompetitive N-methyl-D-aspartic acid receptor antagonists with similar kinetics of block. J Pharmacol Exp Ther 288: 204–210

    PubMed  CAS  Google Scholar 

  262. Blanpied TA, Boeckman FA, Aizenman E, Johnson JW (1997) Trapping channel block of NMDA-activated responses by amantadine and memantine. J Neurophysiol 77: 309–323

    PubMed  CAS  Google Scholar 

  263. Yamakura T, Mori H, Masaki H, Shimoji K, Mishina M (1993) Different sensitivities of NMDA receptor channel subtypes to non-competitive antagonists. NeuroReport 4: 687–690

    PubMed  CAS  Google Scholar 

  264. Urushihara H, Tohda M, Nomura Y (1992) Selective potentiation of N-methyl-D-aspartate-induced current by protein kinase C in Xenopus oocytes injected with rat brain RNA. J Biol Chem 267: 11697–11700

    PubMed  CAS  Google Scholar 

  265. Yuzaki M, Mikoshiba K (1992) Pharmacological and immunocytochemical characterization of metabotropic glutamate receptors in cultured Purkinje cells. J Neurosci 12: 4253–4263

    PubMed  CAS  Google Scholar 

  266. Yamakura T, Mori H, Shimoji K, Mishina M (1993) Phosphorylation of the carboxyl-terminal domain of the zeta 1 subunit is not responsible for potentiation by TPA of the NMDA receptor channel. Biochem Biophys Res Comm 196: 1537–1544

    PubMed  CAS  Google Scholar 

  267. Mori H, Yamakura T, Masaki H, Mishina M (1993) Involvement of the carboxyl-terminal region in modulation by TPA of the NMDA receptor channel. NeuroReport 4: 519–522

    PubMed  CAS  Google Scholar 

  268. Sigel E, Baur R, Malherbe P (1994) Protein kinase C transiently activated heteromeric N-methyl-D-aspartate receptor channels independent of the phosphorylatable C-terminal splice domain and of consensus phosphorylation sites. J Biol Chem 269: 8204–8208

    PubMed  CAS  Google Scholar 

  269. Wang YT, Salter MW (1994) Regulation of NMDA receptors by tyrosine kinases and phosphatases. Nature 369: 233–235

    PubMed  CAS  Google Scholar 

  270. Moon IS, Apperson ML, Kennedy MB (1994) The major tyrosine-phosphorylated protein in the postsynaptic density fraction is N-methyl-D-aspartate receptor subunit 2B. Proc Natl Acad Sci USA 91: 3954–3958

    PubMed  CAS  Google Scholar 

  271. Lau LF, Huganir RL (1995) Differential tyrosine phosphorylation of N-methyl-D-aspartate receptor subunits. J Biol Chem 270: 20036–20041

    PubMed  CAS  Google Scholar 

  272. Yu XM, Salter MW (1998) Gain control of NMDA-receptor currents by intracellular sodium. Nature 396: 469–474

    PubMed  CAS  Google Scholar 

  273. Malenka RC, Ayoub GS, Nicoll RA (1987) Phorbol esters enhance transmitter release in rat hippocampal slices. Brain Res 403: 198–203

    PubMed  CAS  Google Scholar 

  274. Chen L, Huang LY (1991) Sustained potentiation of NMDA receptor-mediated glutamate responses through activation of protein kinase C by a mu opioid. Neuron 7: 319–326

    PubMed  Google Scholar 

  275. Kelso SR, Nelson TE, Leonard JP (1992) Protein kinase C-mediated enhancement of NMDA currents by metabotropic glutamate receptors in Xenopus oocytes. J Physiol (Lond) 449: 705–718

    CAS  Google Scholar 

  276. Snyder GL, Fienberg AA, Huganir RL, Greengard P (1998) A dopamine/D1 receptor/protein kinase A/dopamine-and cAMP-regulated phosphoprotein (Mr 32 kDa)/protein phosphatase-1 pathway regulates dephosphorylation of the NMDA receptor. J Neurosci 18: 10297–10303

    PubMed  CAS  Google Scholar 

  277. Raymond LA (1998) Receptor regulation by phosphorylation. In: AJ Turner, FA Stephenson (eds): Frontiers in neurobiology 3: amino acid neurotransmission. Portland Press, London, 177–194

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ, 07033, USA

    Tony Priestley

Authors
  1. Tony Priestley
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Merck, Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex, CM20 2QR, UK

    Dalip J. S. Sirinathsinghji  & Ray G. Hill  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer Basel AG

About this chapter

Cite this chapter

Priestley, T. (2002). Pharmacology and electrophysiology of excitatory amino acid receptors. In: Sirinathsinghji, D.J.S., Hill, R.G. (eds) NMDA Antagonists as Potential Analgesic Drugs. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8139-5_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-8139-5_2

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9453-1

  • Online ISBN: 978-3-0348-8139-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation