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Diversity and Organization of Excitatory Amino Acid Receptors in the CNS

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Excitatory Amino Acids and Second Messenger Systems

Part of the book series: Schering Foundation Workshop ((SCHERING FOUND,volume 3))

Abstract

Knowledge regarding the anatomical organization of neurotransmitter systems is thought to be critical to understanding the basis of brain function and the action of many drugs. At a first approximation, the anatomical organization of nerve terminals that release excitatory amino acids (EAAs) appears quite simple. Most synapses in the vertebrate CNS that display fast, excitatory transmission probably use an EAA as their neurotransmitter; most synapses that display inhibitory or primarily modulatory transmission do not use an EAA neurotransmitter. Within this simple, ubiquitous distribution of EAA pathways, however, there appears to be a complex organization of multiple, distinct subsystems which differ in their composition of EAA receptors. Since EAA receptor subtypes differ in their physiological and pharmacological properties, as well as their anatomical distributions, the corresponding EAA pathways can be thought of as functionally and pharmacologically distinct EAA systems. Furthermore, in addition to this level of complexity, recent studies have shown that individual EAA receptor types can represent multiple isoforms that can differ in function [1]. Thus, there is considerable potential for both functional and pharmacological diversity which may have many implications for understanding brain function and developing therapeutic agents.

This work was supported by NIH grant NS 28966 and by the Eli Lilly Co.

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References

  1. Sommer B, Keinänen K, Verdoom TA, Wisden W, Burnashev N, Herb A, Köhler 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

    Article  PubMed  CAS  Google Scholar 

  2. Collingridge GL, Lester RAJ (1989) Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacol Rev 40: 143–210

    Google Scholar 

  3. 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. Annu Rev Pharmacol Toxicol 29: 365–402

    Article  PubMed  CAS  Google Scholar 

  4. Watkins JC, Krogsgaard-Larsen P, Honoré T (1990) Structure-activity relationships in the development of excitatory amino acid receptor agonists and competitive antagonists. Trends Pharmacol Sci 11: 25–33

    Article  PubMed  CAS  Google Scholar 

  5. 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

    Article  PubMed  CAS  Google Scholar 

  6. Keinänen 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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Egebjerg J, Bettler B, Hermans-Borgmeyer I, Heinemann S (1991) Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not by AMPA. Nature 351: 745–748

    Article  PubMed  CAS  Google Scholar 

  9. Cotman CW, Bridges RJ, Taube JS, Clark AS, Geddes JW, Monaghan DT (1989) The role of the NMDA receptor in central nervous system plasticity and pathology. J NIH Res 1: 65–74

    Google Scholar 

  10. Rauschecker JP (1991) Mechanisms of visual plasticity: Hebb synapses, NMDA receptors, and beyond. Physiol Rev 71: 587–615

    PubMed  CAS  Google Scholar 

  11. Monaghan DT, Anderson KJ (1991) Heterogeneity and organizaton of excitatory amino acid receptors and transporters. In: Wheal H, Thomson A (eds) Excitatory amino acids and synaptic function. Academic, London, pp 33–54

    Google Scholar 

  12. Fagg GE, Matus A (1984) Selective association of N-methyl aspartate and quisqualate types of L-glutamate receptor with brain postsynaptic densities. Proc Natl Acad Sci USA 81: 6876–6880

    Article  PubMed  CAS  Google Scholar 

  13. Monaghan DT, Cotman CW (1986) Identification and properties of NMDA receptors in rat brain synaptic plasma membranes. Proc Natl Acad Sci USA 83: 7532–7536

    Google Scholar 

  14. Monaghan DT, Cotman CW (1985) Distribution of NMDA-sensitive L-3H-glutamate binding sites in rat brain as determined by quantitative autoradiography. J Neurosci 5: 2909–2919

    PubMed  CAS  Google Scholar 

  15. Maragos WF, Penney JB, Young AB (1988) Anatomic correlation of NMDA and [H]TCP-labelled receptors in rat brain. J Neurosci 8: 493–501

    PubMed  CAS  Google Scholar 

  16. Harris EW, Cotman CW (1986) Long-term potentiation of guinea pig mossy fiber responses in not blocked by N-methyl-D-aspartate antagonists. Neurosci Lett 70: 132–137

    Article  PubMed  CAS  Google Scholar 

  17. Crepel F, Ahanjal SS, Sears TA (1982) Effect of glutamate, aspartate, and related derivatives on cerebellar Purkinje cell dendrites in the rat: an in vitro study. J Physiol (Lond) 329: 297–317

    CAS  Google Scholar 

  18. Fagg GE, Foster AC (1983) Amino acid neurotransmitters and their pathways in the mammalian central nervous system. Neuroscience 9: 701–719

    Article  PubMed  CAS  Google Scholar 

  19. Fonnum F (1984) Glutamate: a neurotransmitter in mammalian brain. J Neurochem 42: 1–11

    Article  PubMed  CAS  Google Scholar 

  20. Cotman CW, Monaghan DT, Ottersen OP, Storm-Mathisen J (1987) Anatomical organization of excitatory amino acid receptors and their pathways Trends Neuro-sci 10: 273–280

    CAS  Google Scholar 

  21. Mayer ML, Westbrook GL (1987) The physiology of excitatory amino acids in the vertebrate central nervous system. Prog Neurobiol 28: 197–276

    Article  PubMed  CAS  Google Scholar 

  22. Monaghan DT, Cotman CW (1986) Anatomical organization of NMDA, kainate and quisqualate receptors. In: Roberts PJ, Storm-Mathisen J, Bradford H (eds) Excitatory amino acids. Macmillan Press, London, pp 279–299

    Google Scholar 

  23. Rassendren F-A, Lory P, Pin J-P, Bockaert J, Nargeot J (1989) A specific quisqualate agonist inhibits kainate responses induced in Xenopus oocytes injected with rat brain RNA. Neurosci Lett 99: 333–339

    Article  PubMed  CAS  Google Scholar 

  24. Zorumski CF, Yang J (1988) AMPA, kainate, and quisqualate activate a common receptor-channel complex on embryonic chick motorneurons. J Neurosci 8: 42774286

    Google Scholar 

  25. Wroblewski JT, Danysz W (1989) Modulation of glutamate receptors: molecular mechanisms and functional implications. Annu Rev Pharmacol Toxicol 29: 441474

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  27. Trombley P, Westbrook G (1990) L-AP4 reduces high threshold calcium currents in olfactory bulb neurons. Soc Neurosci Abstr 16: 547

    Google Scholar 

  28. Schoepp D, Bockaert J, Sladeczek F (1990) Pharmacological and functional characteristics of metabotropic excitatory amino acid receptors. Trends Pharmacol Sci 11: 508–515

    Article  PubMed  CAS  Google Scholar 

  29. Cotman CW, Flatman JA, Ganong AH, Perkins MN (1986) Effects of excitatory amino-acid antagonists on evoked and spontaneous excitatory potentials in guinea-pig hippocampus. J Physiol (Lond) 378: 403–415

    CAS  Google Scholar 

  30. Brose N, Thomas A, Weber MG, Jahn R (1990) A chloride-and calcium-dependent glutamate binding protein from rat brain. Identification as a ubiquitous constituent of the inner mitochondrial membrane. J Biol Chem 265: 10604–10610

    Google Scholar 

  31. Koerner JF, Cotman CW (1981) Micromolar L-2-amino-4-phosphonobutyric acid selectively inhibits perforant path synapses from lateral entorhinal cortex. Brain Res 216: 192–198

    Article  PubMed  CAS  Google Scholar 

  32. Lanthorn TH, Ganong AH, Cotman CW (1984) 2-Amino-4-phosphonobutyrate selectively blocks mossy fiber-CA3 responses in guinea pig but not rat hippo-campus. Brain Res 290: 174–178

    Google Scholar 

  33. Yamamoto C, Sawada S, Takada S (1983) Suppressing action of 2-amino-4-phosphonobutyric acid on mossy fiber-induced excitation in the guinea pig hippo-campus. Exp Brain Res 51: 128–134

    PubMed  CAS  Google Scholar 

  34. Slaughter MM, Miller RF (1981) 2-Amino-4-phosphonobutyric acid: a new pharmacological tool for retina research. Nature 211: 182–185

    Google Scholar 

  35. Collins GGS (1982) Some effects of excitatory amino acid receptor antagonists on synaptic transmission in the rat olfactory cortex slice. Brain Res 244: 311–318

    Article  PubMed  CAS  Google Scholar 

  36. Davies J, Watkins JC (1982) Actions of D and L forms of 2-amino-5-phosphonovalerate and 2-amino-4-phosphonobutyrate in the cat spinal cord. Brain Res 235: 378–386

    Article  PubMed  CAS  Google Scholar 

  37. Hwang PM, Bredt DS, Snyder SH (1990) Autoradiographic imaging of phosphoinositide turnover in the brain. Science 249: 802–804

    Article  PubMed  CAS  Google Scholar 

  38. Cha JJ, Makowiec RL, Penney JB, Young AB (1990) L-[3H]Glutamate labels the metabotropic excitatory amino acid receptor in rodent brain. Neurosci Lett 113: 78–83

    Article  PubMed  CAS  Google Scholar 

  39. Masu M, Tanabe Y, Tsuchida K, Shigemoto R, Nakanishi S (1991) Sequence and expression of a metabotropic glutamate receptor. Nature 349: 760–765

    Article  PubMed  CAS  Google Scholar 

  40. Olverman HJ, Monaghan DT, Cotman CW, Watkins JC (1986) [3H]CPP, a new competitive ligand for NMDA receptors. Eur J Pharmacol 131: 161–162

    Google Scholar 

  41. Monaghan DT, Olverman HJ, Nguyen L, Watkins JC, Cotman CW (1988) Two classes of NMDA recognition sites: differential distribution and differential regulation by glycine. Proc Natl Acad Sci USA 85: 9836–9840

    Article  PubMed  CAS  Google Scholar 

  42. Monaghan DT, Yao D, Olverman HJ, Watkins JC, Cotman CW (1984) Autoradiography of D-[3H]2-amino-5-phosphonopentanoate binding sites in rat brain. Neurosci Lett 52: 253–258

    Article  PubMed  CAS  Google Scholar 

  43. Monaghan DT (1991) Differential stimulation of [3H]MK-801 binding to sub-populations of NMDA receptors. Neurosci Lett 122: 21–24

    Article  PubMed  CAS  Google Scholar 

  44. Monaghan DT, Beaton JA (1991) Quinolinate differentiates between cerebellar and forebrain NMDA receptors. Eur J Pharmacol 194: 123–125

    Article  PubMed  CAS  Google Scholar 

  45. Monaghan DT, Beaton JA (1991) Pharmacologically-distinct NMDA receptor subtypes. Soc Neurosci Abstr 17: 75

    Google Scholar 

  46. Reynolds IJ, Palmer AM (1991) Regional variations in [3H]MK801 binding to rat brain N-methyl-D-aspartate receptors. J Neurochem 56: 1731–1740

    Article  PubMed  CAS  Google Scholar 

  47. Yoneda Y, Ogita K, Enomoto R (1991) Characterization of spermidine-dependent [3H1(+)-5-methyl-I0,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK- 801) binding in brain synaptic membranes treated with Triton X-100. J Pharmacol Exp Ther 256: 1161–1172

    PubMed  CAS  Google Scholar 

  48. O’Shea RD, Manallack DT, Conway EL, Mercer LD, Beart PM (1991) Evidence for heterogenous glycine domains but conserved multiple states of the excitatory amino acid recognition site of the NMDA receptor: regional binding studies with [3H]glycine and [3H]t,-glutamate. Exp Brain Res 86: 652–662

    PubMed  Google Scholar 

  49. Vignon J, Privat A, Chaudieu I, Thierry A, Kamenka JM, Chicheportiche R (1986) [3H]Thienyl-phencyclidine ([3H]TCP) binds to two different sites in rat brain. Localizaton by autoradiography and biochemical techniques. Brain Res 378: 133–141

    Google Scholar 

  50. Quarum M, Parker JD, Keana JEW, Weber E (1990) (+)-[3H]MK-801 binding sites in postmortem human brain. J Neurochem 54: 1163–1168

    Google Scholar 

  51. Sircar R, Zukin SR (1985) Quantitative localization of [3H]TCP binding in rat brain by light microscopic autoradiography. Brain Res 344: 142–145

    Article  PubMed  CAS  Google Scholar 

  52. Jarvis MF, Murphy DE, Williams M (1987) Q3 antitative autoradiographic localization of NMDA receptors in rat brain using [H]CPP: comparison with [3H]TCP binding sites. Eur J Pharmacol 141: 149–152

    Article  PubMed  CAS  Google Scholar 

  53. Sekiguchi M, Okamoto K, Sakai Y (1990) Glycine-insensitive NMDA-sensitive receptor expressed in Xenopus oocytes by guinea pig cerebellar mRNA. J Neuro-sci 10: 2148–2155

    CAS  Google Scholar 

  54. Perkins MN, Stone TW (1983) Quinolinic acid: regional variations in neuronal sensitivity. Brain Res 259: 172–176

    Article  PubMed  CAS  Google Scholar 

  55. Perkins MN, Stone TW (1983) Pharmacology and regional variations of quinolinic acid-evoked excitations in the rat central nervous system. J Pharmacol Exp Ther 226: 551–557

    PubMed  CAS  Google Scholar 

  56. D’ Angelo E, Rossi P, Garthwaite J (1990) Dual-component NMDA receptor currents at a single central synapse. Nature 346: 467–470

    Article  PubMed  Google Scholar 

  57. Zeevalk GD, Nicklas WJ (1990) Action of the anti-ischemic agent ifenprodil on Nmethyl-D-aspartate and kainate-mediated excitotoxicity. Brain Res 522: 135–139

    Article  PubMed  CAS  Google Scholar 

  58. Ornstein PL, Schoepp DD, Leander JD, Lodge D (1991) The development of novel competitive NMDA antagonists as useful therapeutic agents. Discovery of LY 274614 and LY 233536. In: Meldrum BS, Moroni F, Simon RP, Woods JH (eds) Excitatory amino acids. Raven, New York, pp 415–423

    Google Scholar 

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Authors
  1. Daniel T. Monaghan
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  2. Jean A. Beaton
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Editor information

Editors and Affiliations

  1. Department of Neurobiology, The Weizmann Institute of Science, 76100, Rehovot, Israel

    Vivian I. Teichberg

  2. Department of Neuropsychopharmacology, Schering AG, Müllerstraße 170 - 178, P.O. Box 650311, D-1000, Berlin 65, Germany

    Lechoslaw Turski

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© 1991 Springer-Verlag Berlin Heidelberg

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Monaghan, D.T., Beaton, J.A. (1991). Diversity and Organization of Excitatory Amino Acid Receptors in the CNS. In: Teichberg, V.I., Turski, L. (eds) Excitatory Amino Acids and Second Messenger Systems. Schering Foundation Workshop, vol 3. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-22666-7_1

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  • DOI: https://doi.org/10.1007/978-3-662-22666-7_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-22668-1

  • Online ISBN: 978-3-662-22666-7

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