Excitatory amino acid transporters as emerging targets for central nervous system therapeutics

Expert Opinion on Therapeutic Targets

Volumn 3, Issue 4, 1999, Pages 543-570

  Dunlop, John ^a   Zaleska, Margaret M ^a   Eliasof, Scott ^a,b   Moyer, John A ^a  

^a PFIZER INC   (United States)

^b Neurocrine Biosciences   (United States)

Author keywords

amyotrophic lateral sclerosis; drug discovery; EAAT; epilepsy; excitatory amino acid transporter; excitotoxicity; glutamate; ischaemia; neurodegeneration; psychiatric disorders; retina

Indexed keywords

EID: 0000974147     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.3.4.543     Document Type: Review

References (258)

1. FONNUM F: Neurochemical studies on glutamatemediated neurotransmission. In: Excitatory Amino Acids. Meldrum BS, Moroni F, Simon RO, Woods JH (Eds.), Raven Press Ltd., New York, USA (1991):15-25.
2. HAYASHI T: Effects of sodium glutamate on the nervous system. Keio J. Med. (1954) 3:183-192.
3. CURTIS DR, PHILLIS J, WATKINS JC: The chemical excitation of spinal neurons. Nature (1959) 183:611-612.
4. DINGLEDINE R, BORGES K, BOWIE D, TRAYNELIS SF: The glutamate receptor ion channels. Pharmacol. Rev. (1999) 51:7-61. (Pubitemid 29113865)
5. STORM-MATHISEN J, DANBOLT NC, OTTERSEN OP: Localization of glutamate and its membrane transport proteins. In: CNS Neurotransmitters and Neuromodulators: Glutamate. Stone TW (Ed.), CRC Press, Boca Raton, USA (1995):1-18.
6. HOLT WF: Glutamate in health and disease: the role of inhibitors. In: Neuroprotection in CNS Diseases. Bar PR, Beal MF (Eds.), Marcel Dekker, Inc., New York, USA (1997):87-119.
7. FONNUM F, HASSEL B: Glutamate synthesis, metabolism, and uptake. In: CNS Neurotransmitters and Neuromodulators: Glutamate. Stone TW (Ed.), CRC Press, Boca Raton, USA (1995):19-34.
8. NICHOLLS DG: The release of glutamate from synaptic terminals. In: CNS Neurotransmitters and Neuromodulators: Glutamate. Stone TW (Ed.), CRC Press, Boca Raton, USA (1995):35-52.
9. TRUSSELL L: Control of time course of glutamatergic synaptic currents. Prog. Brain Res. (1998) 116:59-69. (Pubitemid 28526928)
10. OTIS TS, WU Y-C, TRUSSELL LO: Delayed clearance of transmitter and the role of glutamate transporters at synapses with multiple release sites. J. Neurosci. (1996) 16:1634-1644. (Pubitemid 26145941)
11. BARBOUR B, KELLER BU, LLANO I, MARTY A: Prolonged presence of glutamate during excitatory synaptic transmission to cerebellar Purkinje cells. Neuron (1994) 12:1331-1343. (Pubitemid 24186800)
12. SARANTIS M, BALLERINI L, MILLER B et al.: Glutamate uptake from the synaptic cleft does not shape the decay of the non-NMDA component of the synaptic current. Neuron (1993) 11:541-549. (Pubitemid 23287081)
13. ISAACSON JS, NICOLL RA: The uptake inhibitor L-trans-PDC enhances responses to glutamate but fails to alter the kinetics of excitatory synaptic currents in the hippocampus. J. Neurophysiol. (1993) 70:2187-2191. (Pubitemid 23351054)
14. TONG G, JAHR CE: Block of glutamate transporters potentiates postsynaptic excitation. Neuron (1994) 13:1195-1203. (Pubitemid 24372137)
15. ASZTELY F, ERDEMLI G, KULLMANN DM: Extrasynaptic glutamate spillover in the hippocampus: dependence on temperature and the role of active glutamate uptake. Neuron (1997) 18:281-93. (Pubitemid 27111110)
16. ENGELSEN BA, MYRSETH E, BORGMANN R et al.: Alterations in excitatory amino acid transmitters in human neurological disease and neuropathology. In: Neurotoxicity of Excitatory Amino Acids. Guidotti A (Ed.), Raven Press Ltd., New York, USA (1990):311-332.
17. INCE PG, EGGETT CJ, SHAW PJ: The role of excitotoxicity in neurological disease. Res. Contemp. Pharmacother. (1997) 8:195-212. (Pubitemid 27485049)
18. MELDRUM BS: The glutamate synapse as a therapeutical target: perspective for the future. Prog. Brain Res. (1998) 116:441-458. (Pubitemid 28526952)
19. OLNEY JW, IKONOMIDOU C: Excitotoxic mechanisms operative in youth and old age. In: Neurobiology of the NMDA Receptor From Chemistry to the Clinic. Kozikowski AP (Ed.) ACH Publishers, Inc., New York, USA (1991):187-202.
20. BAR-PELED O, ROTHSTEIN JD: Anti-glutamate therapies for neurodegenerative disease: the case for amyotrophic lateral sclerosis. In: Cell Death and Diseases of the Nervous System. Koliatsos VE, Ratan RR (Eds.), Humana Press, Totowa, NJ, USA (1999):633-647.
21. LOGAN WJ, SNYDER SH: Unique high affinity uptake systems for glycine, glutamic and aspartic acids in central nervous tissue of the rat. Nature (1971) 234:297-299.
22. BALCAR VJ, JOHNSTON GAR: The structural specificity of the high affinity uptake of L-glutamate and L-aspartate by rat brain slices. J. Neurochem. (1972) 19:2657-2666.
23. BENNETT JP, LOGAN WJ, SNYDER SH: Amino acid neurotransmitter candidates: sodium-dependent high-affinity uptake by a unique synaptosomal fraction. Science (1972) 178:997-999.
24. NICHOLLS D, ATTWELL D: The release and uptake of excitatory amino acids. Trends Pharmacol. Sci. (1990) 11:462-468. (Pubitemid 20351933)
25. SCHOUSBOE A: Transport and metabolism of glutamate and GABA in neurons and glial cells. Int. Rev. Neurobiol. (1981) 22:1-45.
26. FERKANY J, COYLE JT: Heterogeneity of sodiumdependent excitatory amino acid uptake mechanisms in rat brain. J. Neurosci. Res. (1986) 16:491-503. (Pubitemid 17202364)
27. ROBINSON MB, HUNTER-ENSOR M, SINOR J: Pharmacologically distinct sodium-dependent L-[3H]glutamate transport processes in rat brain. Brain Res. (1991) 544:196-202.
28. STORCK T, SCHULTE S, HOFMANN K, STOFFEL W: Structure, expression, and functional analysis of a Na+-dependent glutamate/aspartate transporter from rat brain. Proc. Natl. Acad. Sci. USA (1992) 89:10955-10959.
29. PINES G, DANBOLT NC, BJORAS M et al.: Cloning and expression of a rat brain L-glutamate transporter. Nature (1992) 360:464-467.
30. KANAI Y, HEDIGER MA: Primary structure and functional characterization of a high-affinity glutamate transporter. Nature (1992) 360:467-471.
31. ARRIZA JL, FAIRMAN WA, WADICHE JI et al.: Functional comparisons of three glutamate transporter subtypes cloned from human cortex. J. Neurosci. (1994) 14:5559-5569. (Pubitemid 24279072)
32. FAIRMAN WA, VANDENBERG RJ, ARRIZA JL, KAVANAUGH MP, AMARA SG: An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature (1995) 375:599-603.
33. ARRIZA JL, ELIASOF S, KAVANAUGH MP, AMARA SG: Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc. Natl. Acad. Sci. USA (1997) 94:4155-4160. (Pubitemid 27180515)
34. WAHLE S, STOFFEL W: Membrane topology of the high-affinity L-glutamate transporter (GLAST-1) of the central nervous system. J . Cell Biol. (1996) 135:1867-1877.
35. SEAL RP, AMARA SG: A reentrant loop domain in the glutamate carrier EAAT1 participates in substrate binding and translocation. Neuron (1998) 21:1487-1498. (Pubitemid 29022549)
36. GRUNEWALD M, BENDAHAN A, KANNER BI: Biotinylation of single cysteine mutants of the glutamate transporter GLT-1 from rat brain reveals its unusual topology. Neuron (1998) 21:623-632. (Pubitemid 28475513)
37. ROBINSON MB, DOWD LA: Heterogeneity and functional properties of subtypes of sodiumdependent glutamate transporters in the mammalian central nervous system. Adv. Pharmacol. (1997) 37:69-115.
38. GEGELASHVILI G, SCHOUSBOE A: Cellular distribution and kinetic properties of high-affinity glutamate transporters. Brain Res. Bull. (1998) 43(3):233-238. (Pubitemid 28113004)
39. SEAL RP, AMARA SG: Excitatory amino acid transporters: a family in flux. Ann. Rev. Pharmacol. Toxicol. (1999) 39:431-456. (Pubitemid 29222566)
40. YAMADA H, YATSUSHIRO S, YAMAMOTO A et al.: Functional expression of a GLT-1 type Na+-dependent glutamate transporter in rat pinealocytes. J. Neurochem. (1997) 69:1491-1498. (Pubitemid 27406950)
41. VANDENBERG RJ: Molecular pharmacology and physiology of glutamate transporters in the central nervous system. Clin. Exp. Pharmacol. Physiol. (1998) 25:383-400.
42. DANBOLT NC, CHAUDHRY FA, DEHNES Y et al.: Properties and localization of glutamate transporters. Prog. Brain Res. (1998) 116:23-43. (Pubitemid 28526926)
43. ROTHSTEIN JD, MARTIN L, LEVEY AI et al.: Localization of neuronal and glial glutamate transporters. Neuron (1994) 13:713-725. (Pubitemid 24300175)
44. TORP R, DANBOLT NC, BABAIE E et al.: Differential expression of two glial glutamate transporters in the rat brain: An in situ hybridization study. Eur. J. Neurosci. (1994) 6:936-942. (Pubitemid 24185316)
45. LEHRE KP, LEVY LM, OTTERSEN OP et al.: Differential expression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations. J. Neurosci. (1995) 15:1835-1853.
46. KIRSCHNER MA, COPELAND NG, GILBERT DJ et al.: Mouse excitatory amino acid transporter EAAT2: Isolation, characterization, and proximity to neuroexcitability loci on mouse chromosome 2. Genomics (1994) 24:218-224.
47. NAKAYAMA T, KAWAKAMI H, TANAKA K, NAKAMURA S: Expression of three glutamate transporter subtype mRNAs in human brain regions and peripheral tissues. Mol. Brain Res. (1996) 36:189-192. (Pubitemid 26058892)
48. BERGER UV, HEDIGER MA: Comparative analysis of glutamate transporter expression in rat brain using differential double in situ hybridization. Anat. Embryol. (1998) 198:13-30. (Pubitemid 28333913)
49. MILTON ID, BANNER SJ, INCE PG et al.: Expression of the glial glutamate transporter EAAT2 in the human CNS: an immunohistochemical study. Mol. Brain Res. (1997) 52:17-31. (Pubitemid 27522162)
50. KANAI Y, BHIDE PG, DIFIGLIA M, HEDIGER MA: Neuronal high-affinity glutamate transport in the rat central nervous system. NeuroReport (1995) 6:2357-2362. (Pubitemid 26013125)
51. VELAZ-FAIRCLOTH M, MCGRAW TS, MALANDRO MS et al.: Characterization and distribution of the neuronal glutamate transporter EAAC1 in rat brain. Am. J. Pharmacol. (1996) 270:C67-75.
52. SHASHIDHARAN P, HUNTLEY GW, MURRAY JM et al.: Immunohistochemical localization of the neuronspecific glutamate transporter EAAC1 (EAAT3) in rat brain and spinal cord revealed by a novel monoclonal antibody. Brain Res. (1997) 773:138-148.
53. TORP R, HOOVER F, DANBOLT NC et al.: Differential distribution of the glutamate transporters GLT1 and rEAAC1 in rat cerebral cortex and thalamus: An in situ hybridization analysis. Anat. Embryol. (1997) 195:317-326. (Pubitemid 27156255)
54. FURUTA A, MARTIN LJ, LIN CL et al.: Cellular and synaptic localization of the neuronal glutamate transporters excitatory amino acid transporter 3 and .4. Neuroscience (1997) 81:1031-1042. (Pubitemid 27421767)
55. DEHNES Y, CHAUDHRY FA, ULLENSVANG K et al.: The glutamate transporter EAAT4 in rat cerebellar Purkinje cells: A glutamate-gated chloride channel concentrated near the synapse in parts of the dendritic membrane facing astroglia. J. Neurosci. (1998) 18:3606-3619. (Pubitemid 28225669)
56. KANAI Y, TROTTI D, NUSSBERGER S, HEDIGER MA: The high-affinity glutamate transporter family: structure, function, and physiological relevance. In: Contemporary Neuroscience: Neurotransmitter Transporters: Structure, Function, and Regulation. Reith MEA (Ed.), Humana Press, Totowa, New Jersey, USA (1997):171-213.
57. KIRYU S, YAOGL, MORITA N et al.: Nerve injury enhances rat neuronal glutamate transporter expression: Identification by differential display PCR. J. Neurosci. (1995) 15:7872-7878. (Pubitemid 26006895)
58. YAMACHITA T, KOHMURA E, YUGUCHI T et al.: Changes in glutamate/aspartate transporters (GLAST/GluT-1) mRNA expression following facial nerve transection. Mol. Brain Res. (1996) 38:294-299. (Pubitemid 26168289)
59. LEVY LM, LEHRE KP, WALAAS SI et al.: Down-regulation of glial glutamate transporters after glutamatergic denervation in the rat brain. Eur. J. Neurosci. (1995) 7:2036-2041.
60. SUTHERLAND ML, DELANEY TA, NOEBELS JL: Glutamate transporter mRNA expression in proliferative zones of the developing and adult murine CNS. J. Neurosci. (1996) 16:2191-2207. (Pubitemid 26154331)
61. SHIBATA T, WATANABE W, TANAKA K, WADA K, INOUE Y: Dynamic changes in expression of glutamate transporter mRNAs in developing brain. NeuroReport (1996) 7:705-709. (Pubitemid 26145325)
62. YAMADA K, WATANABE M, SHIBATA T et al.: Glutamate transporter GLT-1 is transiently localised on growing axons of the mouse spinal cord before establishing astrocytic expression. J. Neurosci. (1998) 18:5706-5713. (Pubitemid 28341350)
63. FURUTA A, ROTHSTEIN JD, MARTIN LJ: Glutamate transporter protein subtypes are expressed differentially during rat CNS development. J. Neurosci. (1997) 17:8363-8375. (Pubitemid 27461059)
64. ULLENSVANG K, LEHRE KP, STORM-MATHISEN J, DANBOLT NC: Differential developmental expression of the two rat brain glutamate transporter proteins GLAST and GLT. Eur. J. Neurosci. (1997) 9:1646-1655. (Pubitemid 27348323)
65. BAR-PELED O, BEN-HUR H, BIEGON A et al.: Distribution of glutamate transporter subtypes during human brain development. J. Neurochem. (1997) 69:2571-2580. (Pubitemid 27495445)
66. ITOH M, WATANABE Y, WATANABE M et al.: Expression of a glutamate transporter subtype, EAAT4, in the developing human cerebellum. Brain Res. (1997) 767:265-271. (Pubitemid 27435772)
67. INAGE YW, ITCH M, WADA K, TAKASHIMA S: Expression of two glutamate transporters, GLAST and EAAT4, in the human cerebellum: their correlation in development and neonatal hypoxic-ischemic damage. J. Neuropathol. Exp. Neurol. (1998) 57:554-562.
68. CHAUDHURY F, LEHRE KP, VAN LOOKEREN M et al.: Glutamate transporters in glial plasma membranes: highly differentiated localization revealed by quantitative ultrastructural immunocytochemistry. Neuron (1995) 15:711-720.
69. SCHMITT A, ASAN E, PUSCHEL B, KUGLER P: Cellular and regional distribution of the glutamate transporter GLAST in the CNS of rats: nonradioactive in situ hybridization and comparative immunocytochemistry. J. Neurosci. (1997) 17:1-10. (Pubitemid 27008845)
70. MENNERICK S, DHOND RP, BENZ A et al.: Neuronal expression of the glutamate transporter GLT-1 in hippocampal microcultures. J. Neurosci. (1998) 18:4490-4499. (Pubitemid 28280160)
71. CONTI F, DEBIASI S, MINELLI A, ROTHSTEIN JD, MELONE M: EAAC1, a high-affinity glutamate transporter, is localised to astrocytes and gabaergic neurones besides pyramidal cells in the rat cerebral cortex. Cerebral Cortex (1998) 8:108-116. (Pubitemid 28134393)
72. LEHRE KP, DANBOLT NC: The number of glutamate transporter subtype molecules at glutamatergic synapses: chemical and stereological quantification in young adult rat brain. J. Neurosci. (1998) 18:8751-8757. (Pubitemid 28491741)
73. RAUEN T, ROTHSTEIN JD, WASSLE H: Differential expression of three glutamate transporter subtypes in the rat retina. Cell Tissue Res. (1996) 286:325-336. (Pubitemid 26418041)
74. CHOI I, CHIU SY: Expression of high-affinity neuronal and glial glutamate transporters in the rat optic nerve. Glia (1997) 20:184-192. (Pubitemid 27324304)
75. ELIASOF S, ARRIZA JL, LEIGHTON BH et al.: Excitatory amino acid transporters of the salamander retina: identification, localization, and function. J. Neurosci. (1998) 18:698-712. (Pubitemid 28041906)
76. DUNLOP J, MCILVAIN HB, LOU Z, FRANCO R: The pharmacological profile of L-glutamate transport in human NT2 neurones is consistent with excitatory amino acid transporter 2. Eur. J. Pharmacol. (1998) 360:249-256. (Pubitemid 28529192)
77. TAN J, ZELENAIA O, CORREALE D, ROTHSTEIN JD, ROBINSON MB: Expression of the GLT-1 subtype of Na+-dependent glutamate transporter: pharmacological characterization and lack of regulation by protein kinase C. J. Pharm. Exp. Ther. (1999) 289:1600-1610. (Pubitemid 29246696)
78. VANDENBERG RJ, MITROVIC AD, CHEBIB M, BALCAR VJ, JOHNSTON GA: Contrasting modes of action of methylglutamate derivatives on the excitatory amino acid transporters, EAAT1 and EAAT2. Mol. Pharmacol. (1997) 51:809-815. (Pubitemid 27224686)
79. SHIMAMOTO K, LEBRUN B, YASUDA-KAMATANI Y et al.: DL-threo-beta-benzyl- oxyaspartate, a potent blocker of excitatory amino acid transporters. Mol. Pharmacol. (1998) 53:195-201. (Pubitemid 28099728)
80. BRIDGES RJ, STANLEY MS, ANDERSON MW, COTMAN CW, CHAMBERLIN AR: Conformationally defined neurotransmitter analogues. Selective inhibition of glutamate uptake by one pyrrolidine-2,4-dicarboxylate diastereomer. J. Med. Chem. (1991) 34:717-725.
81. BRIDGES RJ, LOVERING FE, KOCH H, COTMAN CW, CHAMBERLIN AR: A conformationally constrained competitive inhibitor of the sodium-dependent glutamate transporter in forebrain synaptosomes: L-anti-endo-3,4- methanopyrrolidine dicarboxylate. Neurosci. Lett. (1994) 174:193-197.
82. NAKAMURA Y, KATAOKA K, ISHIDA M, SHINOZAKI H: (2S,3S,4R)-2- (carboxycyclopropyl)glycine, a potent and competitive inhibitor of both glial and neuronal uptake of glutamate. Neuropharmacology (1993) 32:833-837. (Pubitemid 23265302)
83. BRIDGES RJ, KAVANAUGH MP, CHAMBERLIN AR: A pharmacological review of competitive inhibitors and substrates of high-affinity, sodium-dependent glutamate transport in the central nervous system. Curr. Pharm. Des. (1999) 5:363-379. (Pubitemid 29238997)
84. KANNER BI, SCHULDINER S: Mechanism of transport and storage of neurotransmitters. CRC Crit. Rev. Biochem. (1987) 22:1-38.
85. ERECINSKA M: The neurotransmitter amino acid transport systems. A fresh outlook on an old problem. Biochem. Pharmacol. (1987) 36:3547-55. (Pubitemid 18068302)
86. KANNER BI, SHARON I: Active transport of L-glutamate by membrane vesicles isolated from rat brain. Biochemistry (1978) 17:3949-3953. (Pubitemid 9036507)
87. SZATKOWSKI M, BARBOUR B, ATTWELL D: The potassium-dependence of excitatory amino acid transport: resolution of a paradox. Brain Res. (1991) 555:343-345.
88. ATTWELL D, BARBOUR B, SZATKOWSKI M: Nonvesicular release of neurotransmitter. Neuron (1993) 11:401-407. (Pubitemid 23287068)
89. STALLCUP WB, BULLOCH K, BAETGE EE: Coupled transport of glutamate and sodium in a cerebellar nerve cell line. J. Neurochem. (1979) 32:57-65. (Pubitemid 9108930)
90. BARBOUR B, BREW H, ATTWELL D: Electrogenic glutamate uptake in glial cells is activated by intracellular potassium. Nature (1988) 335:433-435.
91. ELIASOF S, WERBLIN F: Characterization of the glutamate transporter in retinal cones of the tiger salamander. J. Neurosci. (1993) 13:402-411. (Pubitemid 23028752)
92. ZERANGUE N, KAVANAUGH MP: Flux coupling in a neuronal glutamate transporter. Nature (1996) 383:634-637. (Pubitemid 26347587)
93. LEVY LM, WARR O, ATTWELL D: Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. J. Neurosci. (1998) 18:9620-9628. (Pubitemid 28543743)
94. OTIS TS, JAHR CE: Anion currents and predicted glutamate flux through a neuronal glutamate transporter. J. Neurosci. (1998) 18:7099-7110. (Pubitemid 28425797)
95. WADICHE JI, KAVANAUGH MP: Macroscopic and microscopic properties of a cloned glutamate transporter/chloride channel. J. Neurosci. (1998) 18:7650-7661. (Pubitemid 28441007)
96. BERGLES DE, JAHR CE: Synaptic activation of glutamate transporters in hippocampal astrocytes. Neuron (1997) 19:1297-1308. (Pubitemid 28030548)
97. ERECINSKA M, WANTORSKY D, WILSON DF: Aspartate transport in synaptosomes from rat brain. J. Biol. Chem. (1983) 258:9069-9077. (Pubitemid 13035573)
98. NELSON PJ, DEAN GE, ARONSON PS, RUDNICK G: Hydrogen ion cotransport by the renal brush border glutamate transporter. Biochemistry (1983) 22:5459-5463. (Pubitemid 14240200)
99. WADICHE JI, VANDENBERG RJ, ARRIZA JL, AMARA SG, KAVANAUGH MP: Ligand-gated chloride conductance associated with a human glutamate transporter. Biophys. J. (1995) 68:A437.
100. WADICHE JI, AMARA SG, KAVANAUGH MP: Ion fluxes associated with excitatory amino acid transport. Neuron (1995) 15:721-728.
101. BILLUPS B, ROSSI D, ATTWELL D: Anion conductance behavior of the glutamate uptake carrier in salamander retinal glial cells. J. Neurosci. (1996) 16:6722-6731. (Pubitemid 26359356)
102. OTIS TS, KAVANAUGH MP, JAHR CE: Postsynaptic glutamate transport at the climbing fiber-Purkinje cell synapse. Science (1997) 277:1515-1518. (Pubitemid 27449241)
103. ELIASOF S, JAHR CE: Retinal glial cell transporter is coupled to an anionic conductance. Proc. Natl. Acad. Sci. USA (1996) 93:4153-4158.
104. PICAUD SA, LARSSON HP, WELLIS DP, LECAR H, WERBLIN FS: Cone photoreceptors respond to their own glutamate release in the tiger salamander. Proc. Natl. Acad. Sci. USA (1995) 92:9417-9421.
105. GRANT GB, DOWLING JE: A glutamate-activated chloride current in cone-driven ON bipolar cells of the white perch retina. J. Neurosci. (1995) 15:3852-3862.
106. SCHWARTZ EA, TACHIBANA M: Electrophysiology of glutamate and sodium co-transport in a glial cell of the salamander retina. J. Physiol. (1990) 426:43-80. (Pubitemid 20224776)
107. VANDENBERG RJ, ARRIZA JL, AMARA SG, KAVANAUGH MP: Constitutive ion fluxes and substrate binding domains of human glutamate transporters. J. Biol. Chem. (1995) 270:17668-17671.
108. FAIRMAN WA, SONDERS MS, MURDOCH GH, AMARA SG: Arachidonic acid elicits a substrate-gated proton current associated with the glutamate transporter EAAT4. Nature Neurosci. (1998) 1:105-113.
109. TZINGOUNIS AV, LIN CL, ROTHSTEIN JD, KAVANAUGH MP: Arachidonic acid activates a proton conductance in the rat glutamate transporter EAAT4. J. Biol. Chem. (1998) 273:17315-17317. (Pubitemid 28355055)
110. GEGELASHVILI G, CIVENNI G, RACAGNI G et al.: Glutamate receptor agonists up-regulate glutamate transporter GLAST in astrocytes. NeuroReport (1996) 8:261-265. (Pubitemid 126785570)
111. GEGELASHVILI G, DANBOLT NC, SCHOUSBOE A: Neuronal soluble factors differentially regulate the expression of the GLT-1 and GLAST glutamate transporters in cultured astroglia. J. Neurochem. (1997) 69:2612-2615. (Pubitemid 27495450)
112. SWANSON RA, LIU J, MILLER JW et al.: Neuronal regulation of glutamate transporter subtype expression in astrocytes. J. Neurosci. (1997) 17:932-940. (Pubitemid 27043952)
113. SCHLAG BD, VONDRASEK JR, MUNIR M et al.: Regulation of the glial Na+-dependent glutamate transporters by cyclicAMPanalogs and neurons. Mol. Pharmacol. (1998) 53:355-369. (Pubitemid 28162855)
114. CASADO M, BENDAHAN A, ZAFRA F et al.: Phosphorylation and modulation of brain glutamate transporters by protein kinase C. J. Biol. Chem. (1993) 268:27313-27317. (Pubitemid 24006452)
115. GANEL R, CROSSON CE: Modulation of human glutamate transporter activity by phorbol ester. J. Neurochem. (1998) 70:993-1000. (Pubitemid 28113631)
116. CONRADT M, STOFFEL W: Inhibition of the high-affinity brain glutamate transporter GLAST-1 via direct phosphorylation. J. Neurochem. (1997) 68:1244-1251. (Pubitemid 27086230)
117. DOWD LA, ROBINSON MB: Rapid stimulation of EAAC1-mediated Na+-dependent L-glutamate transport activity in C6 glioma cells by phorbol ester. J. Neurochem. (1996) 67:508-516. (Pubitemid 26255643)
118. DAVIES KE, STRAFF DJ, WEINSTEIN EA et al.: Multiple signaling pathways regulate cell surface expression and activity of the excitatory amino acid carrier 1 subtype of Glu transporter in C6 glioma. J. Neurosci. (1998) 18:2475-2485. (Pubitemid 28141796)
119. ZERANGUE N, ARRIZA JL, AMARA SG, KAVANAUGH MP: Differential modulation of human glutamate transporter subtypes by arachidonic acid. J. Biol. Chem. (1995) 270:6433-6435.
120. VOLTERRA A, TROTTI D, CASSUTTI P et al.: High sensitivity of glutamate uptake to extracellular free arachidonic acid levels in rat cortical synaptosomes and astrocytes. J. Neurochem. (1992) 59:600-606.
121. TROTTI D, VOLTERRA A, LEHRE KP et al.: Arachidonic acid inhibits a purified and reconstituted glutamate transporter directly from the water phase and not via the phospholipid membrane. J. Biol. Chem. (1995) 270:9890-9895.
122. SPIRIDON M, KAMM D, BILLUPS B, MOBBS P, ATTWELL D: Modulation by zinc of the glutamate transporters in glial cells and cones isolated from the tiger salamander retina. J. Physiol. (1998) 506:363-376. (Pubitemid 28048366)
123. VANDENBERG RJ, MITROVIC AD, JOHNSTON GA: Molecular basis for differential inhibition of glutamate transporter subtypes by zinc ions. Mol. Pharmacol. (1998) 54:189-196. (Pubitemid 28337602)
124. FAIRMAN WA, VANDENBERG RJ, AMARA SG: Modulation of the excitatory amino acid transporters EAAT1-5 by zinc. Soc. Neurosci. Abstr. (1998) 24:2072.
125. TROTTI D, DANBOLT NC, VOLTERRA A: Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration. Trends Pharmacol. Sci. (1998) 19:328-334. (Pubitemid 28389731)
126. BERMAN SB, HASTINGS TG: Inhibition of glutamate transport in synaptosomes by dopamine oxidation and reactive oxygen species. J. Neurochem. (1997) 69:1185-1195. (Pubitemid 27364840)
127. LIPTON SA, ROSENBERG PA: Mechanisms of disease: excitatory amino acids as a common pathway for neurologic disorders. New Engl. J. Med. (1994) 330:613-622.
128. COYLE JT, PUTTFARCKEN P: Oxidative stress, glutamate and neurodegenerative disease. Science (1993) 262:689-695. (Pubitemid 23350687)
129. MASSIEU L, GARCIA O: The role of excitotoxicity and metabolic failure in the pathogenesis of neurological disorders. Neurobiol. (1998) 6:99-108. (Pubitemid 29113099)
130. BILLUPS B, ROSSI D, OSHIMA T et al.: Physiological and pathological operation of glutamate transporters. Prog. Brain Res. (1998) 116:45-57. (Pubitemid 28526927)
131. TAKAHASHI M, BILLUPS B, ROSSI D et al.: The role of glutamate transporters in glutamate homeostasis in the brain. J. Exp. Biol. (1997) 200:401-409. (Pubitemid 27126472)
132. IKONOMIDOU C, TURSKI L: Neurodegenerative disorders: Clues from glutamate and energy metabolism. Crit. Rev. Neurobiol. (1996) 10:239-263. (Pubitemid 27033853)
133. ROTHSTEIN JD: Excitotoxicity and neurodegeneration in amyotrophic lateral sclerosis. Clin. Neurosci. (1996) 3:348-359.
134. MASLIAH E, ALFORD M, DETERESA R et al.: Deficient glutamate transport is associated with neurodegeneration in Alzheimer's disease. Ann. Neurol. (1996) 40:759-766. (Pubitemid 26415188)
135. MURRAY AM, SHANNON WEICKERT C, SHASHIDHARAN P, HYDE TM, KLEINMAN JE: Decreased neuron-specific excitatory amino acid transporter 3 (EAAT3) in schizophrenic hippocampus. Soc. Neurosci. Abstr. (1996) 22:1680.
136. SCHNEIDER JS, WADE T, LIDSKY TI: Chronic neuroleptic treatment alters expression of glial glutamate transporter GLT-1 mRNA in the striatum. NeuroReport (1998) 9:133-136. (Pubitemid 28046668)
137. ROTHMAN SM: Synaptic release of excitatory amino transmitter mediates anoxic neuronal death. J. Neurosci. (1984) 4:1884-1891.
138. CHOI DW: Excitotoxic cell death. J. Neurobiol. (1992) 23:1261-1276.
139. PALMER AM: Excitatory amino acid neurons and receptors in Alzheimer's disease. In: Neurobiology of the NMDA Receptor: From Chemistry to the Clinic. Kozikowski AP (Ed.), VCH Publishers, Inc., New York, USA (1991):203-237.
140. ROSENBERG PA, AIZENMAN E: Hundred-fold increase in neuronal vulnerability to glutamate toxicity in astrocyte-poor cultures of a rat cerebral cortex. Neurosci. Lett. (1989) 103:162-168. (Pubitemid 19201246)
141. FREUND WD, GRIESHOP B, NEUMAN U, REDDIG S: Glutamate-induced calcium responses in rat primary cortical cultures are potentiated by co-administration of glutamate transport inhibitors. Neurosci. Lett. (1995) 188:61-64.
142. MCBEAN GJ, ROBERTS PJ: Neurotoxicity of L-glutamate and DL-threo-3-hydroxyaspartate in the rat striatum. J. Neurochem. (1985) 44:247-254. (Pubitemid 15190148)
143. ROBINSON MD, DJALI S, BUCHHALTER JR: Inhibition of glutamate uptake with L-trans-pyrrolidine-2,4,-dicarboxylate potentiates glutamate toxicity in primary hippocampal cultures. J. Neurochem. (1993) 61:2099-2103. (Pubitemid 23354066)
144. ROTHSTEIN JD, JIN L, DYKES-HOBERG M, KUNCL RW: Chronic glutamate uptake inhibition produces a model of slow neurotoxicity. Proc. Natl. Acad. Sci. USA (1993) 90:6591-6595. (Pubitemid 23207259)
145. VORNOV JJ, TASKER RC, PARK J: Neurotoxicity of acute glutamate transport blockade depends on coactivation of both NMDA and AMPA/kainate receptors in organotypic hippocampal cultures. Exp. Neurol. (1995) 133:7-17.
146. WANG GI, CHUNG HJ, SCHNUER JA et al.: Dihydrokainate-sensitive neuronal glutamate transport is required for protection of rat cortical neurons in culture against synaptically released glutamate. Eur. J. Neurosci. (1998) 10:2523-2531. (Pubitemid 28362560)
147. ROTHSTEIN JD, DYKES-HOBERG M, PARDO CA et al.: Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron (1996) 16:675-686. (Pubitemid 26103145)
148. TANAKA K, WATASE K, MANABE T et al.: Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science (1997) 267:1699-1702. (Pubitemid 27421977)
149. SUTHERLAND M: The role of glutamate transport in seizure-induced excitotoxic cell death: A new transgenic model. Epilepsia (1998) 39(Suppl.6):62.
150. WATASE K, HASHIMOTO K, KANO M et al.: Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice. Eur. J. Neurosci. (1998) 10:976-988. (Pubitemid 28375622)
151. PEGHINI P, JANSEN J, STOFFEL W: Glutamate transporter EAAC-1-deficient mice develop dicarboxylic aminoaciduria and behavioural abnormalities but no neurodegeneration. EMBO J. (1997) 16:3822-3832. (Pubitemid 27280998)
152. SHAYAKUL C, KANAI Y, LEE WS et al.: Localization of the high-affinity glutamate transporter EAAC1 in rat kidney. Am. J. Physiol. (1997) 273:F1023-1029.
153. CHOI DW, ROTHMAN SM: The role of glutamate neurotoxicity in hypoxy-ischaemic neuronal death. Ann. Rev. Neurosci. (1990) 13:177-182.
154. SZATKOWSKI M, ATTWELL D: Triggering and execution of neuronal death in brain ischaemia: Two phases of glutamate release by different mechanisms. Trends Neurosci. (1994) 17:359-365. (Pubitemid 24256070)
155. BULLOCK R, ZAUNER A, WOODWARD J, YOUNG HF: Massive persistent release of excitatory amino acids following human stroke. Stroke (1995) 26:2187-2189.
156. CASTILLO J, DAVALOS A, NOYA M: Progression of ischaemic stroke and excitotoxic amino acids. Lancet (1997) 349:79-83. (Pubitemid 27023423)
157. FOSTER AC, FAGG GE: Neurobiology: taking apart NMDA receptors. Nature (1987) 329:395-396.
158. CHOI DW: Ionic dependence of glutamate neurotoxicity. J. Neurosci. (1987) 7:369-379. (Pubitemid 17017466)
159. DUGAN LL, CHOI DW: Excitotoxicity, free radicals and cell membrane changes. Ann. Neurol. (1994) 35:S17-S21. (Pubitemid 24153859)
160. NICOTERA P, LIPTON SA: Excitotoxins in neuronal apoptosis and necrosis. J. Cereb. Blood Flow Metab. (1999) 19:583-591. (Pubitemid 30161210)
161. LEE JM, ZIPFEL GJ, CHOI DW: The changing landscape of ischaemic brain injury mechanisms. Nature (1999) 399:A7-A14. (Pubitemid 29295654)
162. DREJER J, BENVENISTE H, DIEMER NH, SCHOUSBOE A: Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro. J. Neurochem. (1985) 45:145-151. (Pubitemid 15046087)
163. WAHL F, OBRENOVITCH TP, HARDY A et al.: Altered glutamatergic transmission in neurological disorders: from high extracellular glutamate to excessive synaptic efficacy. Prog. Neurobiol. (1997) 51:39-87. (Pubitemid 27080814)
164. SZATOWSKI M, BARBOUR B, ATTWELL D: Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake. Nature (1990) 348:443-446. (Pubitemid 120015084)
165. LONGUEMARE MC, SWANSON RA: Excitatory amino acid release from astrocytes during energy failure by reversal of sodium-dependent uptake. J. Neurosci. Res. (1995) 40:379-385.
166. GEMBA T, OSHIMA T, NINOMIYA M: Glutamate efflux via the reversal of the sodium-dependent glutamate transporter caused by glycolytic inhibition in rat cultured astrocytes. Neuroscience (1994) 63:789-795. (Pubitemid 24360231)
167. ROETTGER V, LIPTON P: Mechanism of glutamate release from rat hippocampal slices during in vitro ischemia. Neuroscience (1996) 75:677-685. (Pubitemid 26377040)
168. KOCH HP, CHAMBERLAIN AR, BRIDGES RJ: Non-transportable inhibitors attenuate reversal of glutamate uptake in synaptosomes following a metabolic insult. Mol. Pharmacol. (1999) 55:1044-1048. (Pubitemid 29252370)
169. PHYLLIS JW, SMITH-BARBOUR M, PERKINS LM, O'REGAN MH: Characterisation of glutamate, aspartate and GABA release from ischaemic rat cerebral cortex. Brain Res. Bull. (1994) 34:457-466. (Pubitemid 24180630)
170. DAWSON LA, DJALI S, GONZALES C, VINEGRA MA, ZALESKA MM: Characterization of transient focal ischemia-induced increases in extracellular glutamate and aspartate: contribution of reversal of the GLT-1 transporter. J. Neurochem. (1999) Submitted.
171. SEKI Y, FEUSTEL J, KELLER RW, TRANMER BI, KIMELBERG HK: Inhibition of ischemia-induced glutamate release in rat striatum by dihydrokainate and an anion channel blocker. Stroke (1999) 30:433-440. (Pubitemid 29071814)
172. OTORI Y, SHIMADA S, TANAKA K et al.: Marked increase in glutamate-aspartate transporter (GLAST/GluT-1) mRNA following transient retinal ischemia. Mol. Brain Res. (1994) 27:310-314. (Pubitemid 24379214)
173. HARADA T, HARADA C, MATANABE Met al.: Functions of the two glutamate transporters GLAST and GLT-1 in the retina. Proc. Natl. Acad. Sci. USA (1998) 95:4663-4666. (Pubitemid 28207970)
174. FUJITA H, SATO K, WEN T-C, PENG Y, SAKANAKA M: Differential expressions of glycine transporter 1 and three glutamate transporter mRNA in the hippocampus of gerbils with transient forebrain ischemia. J. Cereb. Blood Flow Metab. (1999) 19:604-615. (Pubitemid 30161212)
175. TORP R, LEKIEFFRE D, LEVY LM et al.: Reduced postischemic expression of a glial glutamate transporter, GLT1, in the rat hippocampus. Exp. Brain Res. (1995) 103:51-58.
176. YAN YP, YIN KJ, SUN FY: Effect of glutamate transporter on neuronal damage induced by photochemical thrombotic brain ischemia. NeuroReport (1998) 9:441-446.
177. FADEN AI, DEMEDIUK P, PANTER SS, VINK R: The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science (1989) 244:798-800. (Pubitemid 19163864)
178. KATOH H, SIMA K, NAWASHIRO H, WADA K, CHIGASAKI H: The effect of MK-801 on extracellular neuroactive amino acids in hippocampus after closed head injury followed by hypoxia in rats. Brain Res. (1997) 758:731-769.
179. MCINTOSH TK, JUHLER M, WIELOD T: Novel pharmacologic strategies in the treatment of experimental traumatic brain injury. J. Neurotrauma (1998) 15:731-769. (Pubitemid 28487990)
180. ALLESANDRI B, BULLOCK R: Glutamate and its receptors in the pathophysiology of brain and spinal cord injuries. Prog. Brain Res. (1998) 116:303-330. (Pubitemid 28526943)
181. PALMER AM, MARION DW, BOTSCHELLER ML, SWEDLOW PE, STYREN SD, DEKOSKY ST: Traumatic brain injuryinduced excitotoxicity assessed in a controlled cortical impact model. J . Neurochem. (1993) 61:2015-2024. (Pubitemid 23354056)
182. GLOBUS NYT, ALONSO O, DIETRICH WD, BUSTO R, GINSBERG MD: Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia. J. Neurochem. (1995) 65:1704-1711.
183. KATAYAMA V, BECKER DP, TAMURA T, HOVADA DA: Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J. Neurosurg. (1990) 73:889-900.
184. KOURA SS, DOPPENBERG EMR, MARMAROU A et al.: Relationship between excitatory amino acid release and outcome after severe human head injury. Acta Neurochir. (1998) 71:244-246. (Pubitemid 128444409)
185. PALMER AM, MARION DW, BOTSCHELLER ML, BOWEN DM, DEKOSKY ST: Increased transmitter amino acids concentrations in human ventricular CSF after brain trauma. NeuroReport (1994) 6:153-156.
186. BULLOCK R, ZAUNER A, MYSEROS JS et al.: Evidence for prolonged release of excitatory amino acids in severe human head trauma-relationship to clinical events. Ann. NY Acad. Sci. (1995) 11:290-298.
187. ZAUNER A, BULLOCK R: The role of excitatory amino acids in severe brain trauma: opportunities for therapy: a review. J. Neurotrauma (1995) 12:547-554.
188. RAO VLR, BASKAYA M, DOGAN A, ROTHSTEIN JD, DEMPSEY RJ: Traumatic brain injury down-regulates glial glutamate transporter (GLT-1 and GLAST) proteins in rat brain. J. Neurochem. (1998) 70:2020-2027. (Pubitemid 28207826)
189. MA X, XIA Y, YAN HQ et al.: Increased expression of neuronal glutamate transporter protein (EAAC1) after traumatic brain injury (TBI) in rats. J. Neurotrauma (1998) 15:882.
190. BENDER AS, NORENBERG MD: Effect of trauma on cell volume and glutamate uptake in cultured astrocytes. J. Neurotrauma (1998) 15:858.
191. SULLIVAN PG, KELLER JN, MATTSON MP, SCHEFF SW: Traumatic brain injury alters synaptic homeostasis: implications for impaired mitochondrial and transport function. J. Neurotrauma (1998) 15:789-798. (Pubitemid 28487993)
192. TENG Y, WRATHALL J: Local blockade of sodium channels by tetrodotoxin ameliorates tissue loss and long-term functional deficits resulting from experimental spinal cord injury. J. Neurosci. (1997) 17:4359-4366. (Pubitemid 27220626)
193. STYS PK: Anoxic and ischemic injury of myelinated axons in CNS white matter: from mechanistic concepts to therapeutics. J. Cereb. Blood Flow Metab. (1998) 18:2-25. (Pubitemid 28019008)
194. LI S, MEALING GAR, MORLEY P, STYS PK: Novel injury mechanism in anoxia and trauma of spinal cord white matter: Glutamate release via reverse Na+-dependent glutamate transport. J. Neurosci. (1999) 19:1-9.
195. BEAL MF: Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative disease? Ann. Neurol. (1992) 31:119-130.
196. NOVELLI A, REILLY JA, LYSKO PC, HENNEBERRY RC: Glutamate becomes neurotoxic via theNMDAreceptor when intracellular energy levels are reduced. Brain Res. (1988) 451:205-212.
197. SCHOR NF: Inactivation of mammalian brain glutamic synthetase by oxygen radicals. Brain Res. (1988) 456:17-21.
198. SANCHEZ-CARBENTE MD, MASSIEU L: Transient inhibition of glutamate uptake in vivo induces neurodegeneration when energy metabolism is impaired. J. Neurochem. (1999) 72:129-138. (Pubitemid 29013886)
199. ROSEN DR, SIDDIGUE T, PATTERSON D et al.: Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature (1993) 362:59-62. (Pubitemid 23087289)
200. PLAITAKIS A, CONSTANTAKAKIS E, SMITH J: The neuroexcitotoxic amino acids glutamate and aspartate are altered in the spinal cord and brain in amyotrophic lateral sclerosis. Ann. Neurol. (1988) 24:446-449.
201. SHAW PJ, FORREST V, INCE PG, RICHARDSON JP, WASTELL HJ: CSF and plasma amino acid levels in motor neuron disease: Elevation of CSF glutamate in a subset of patients. Neurodegeneration (1995) 4:209-216.
202. ROTHSTEIN JD, MARTIN LJ, KUNCL RW: Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. New Engl. J. Med. (1992) 326:1464-1468.
203. ROTHSTEIN JD, VANKAMMEN M, LEVEY AI, MARTIN LJ, KUNCL RW: Selective loss of glial glutamate transporter GLT-1 amyotrophic lateral sclerosis. Ann. Neurol. (1995) 38:73-84.
204. BRISTOL LA, ROTHSTEIN JD: Glutamate transporter gene expression in amyotrophic lateral sclerosis motor cortex. Ann. Neurol. (1996) 39:676-679. (Pubitemid 26143607)
205. LIN C-L G, BRISTOL LA, JIN L et al.: Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis. Neuron (1998) 20:589-602. (Pubitemid 28153087)
206. WONG PC, ROTHSTEIN JD, PRICE DL: The genetic and molecular mechanisms of motor neuron disease. Curr. Opin. Neurobiol. (1998) 8:791-799. (Pubitemid 28564478)
207. PEDERSEN WA, FU W, KELLER JN et al.: Protein modification by the lipid peroxidation product 4-Hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients. Ann. Neurol. (1998) 44:819-824. (Pubitemid 28516055)
208. TROTTI D, ROLFS A, DANBOLT NC, BROWN RH, JR., HEDIGER MA: SOD1 mutants linked to amyotrophic lateral sclerosis selectively inactivate a glial glutamate transporter. Nature Neurosci. (1999) 2:427-433. (Pubitemid 30491252)
209. ROTHSTEIN JD, KUNCL RW: Neuroprotective strategies in a model of chronic glutamate-mediated motor neuron toxicity. J. Neurochem. (1995) 65:643-651.
210. SCOTT HL, TANNENBERG AE, DODD PR: Variant forms of neuronal glutamate transporter sites in Alzheimer's disease cerebral cortex. J. Neurochem. (1995) 64:2193-2202.
211. LI S, MALLORY M, ALFORD M, TANAKA S, MASLIAH E: Glutamate transporter alterations in Alzheimer's disease are possibly associated with abnormal APP expression. J. Neuropathol. Exp. Neurol. (1997) 56:910-911.
212. MASLIAH E: Mechanism of synaptic pathology in Alzheimer's disease. J. Neural. Transm. (1998) 53:147-158. (Pubitemid 28361776)
213. BECKSTROM H, JULSRUD L, HAUGETO Oet al.: Interindividual differences in the levels of the glutamate transporters GLAST and GLT, but no clear correlation with Alzheimer's disease. J. Neurosci. Res. (1999) 55:218-229. (Pubitemid 29056962)
214. GRAY CW, PATEL AJ: Neurodegeneration mediated by glutamate and b-amyloid peptide: a comparison and possible interaction. Brain Res. (1995) 691:169-179.
215. HARRIS ME, WANG Y, PEDCIGO NW et al.: Amyloid b-peptide (25-35) inhibits Na+-dependent glutamate uptake in rat hippocampal astrocyte cultures. J. Neurochem. (1996) 67:277-286. (Pubitemid 26185607)
216. HARRIS ME, CARNEY JM, COLE PS et al.: b-amyloid peptide-derived, oxygen-dependent free radicals inhibit glutamate uptake in cultured astrocytes: implications for Alzheimer's disease. NeuroReport (1995) 6:1875-1879.
217. KELLER JN, PANG Z, GEDDES JW et al.: Impairment of glucose and glutamate transport and induction of mitochondrial oxidative stress and dysfunction in synaptosomes by amyloid beta-peptide: role of the lipid peroxidation product 4-hydroxynonenal. J. Neurochem. (1997) 69:273-284. (Pubitemid 27274182)
218. MASLIAH E, MALLORY M, ALFORD M, TANAKA S, HANSEN LA: Caspase dependent DNA fragmentation might be associated with excitotoxicity in Alzheimer's disease. J. Neuropathol. Exp. Neurol. (1998) 57:1041-1052. (Pubitemid 28525451)
219. SUCHER NJ, LIPTON SA, DREYER EB: Molecular basis of glutamate toxicity in retinal ganglion cells. Vision Res. (1997) 37:3483-3493. (Pubitemid 27491629)
220. DREYER EB, ZURAKOWSKI D, SCHUMER RA, PODOS SM, LIPTON SA: Elevated glutamate levels in the vitreous body of humans and monkeys with glaucoma. Arch. Ophthalmol. (1996) 114:299-305. (Pubitemid 26086736)
221. RAUEN T, KANNER BI: Localization of the glutamate transporter GLT-1 in rat and macaque monkey retinae. Neurosci. Lett. (1994) 169:137-140.
222. DEROUICHE A, RAUEN T: Coincidence of L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS) immunoreactions in retinal glia: evidence for coupling of GLAST and GS in transmitter clearance. J. Neurosci. Res. (1995) 42:131-143.
223. SCHEYER RD: Involvement of glutamate in human epileptic activities. Prog. Brain Res. (1998) 116:359-370.
224. JOHNSTON D, BROWN TH: Giant synaptic potential hypothesis for epileptiform activity. Science (1981) 211:294-297. (Pubitemid 11131079)
225. GODDARD GV, MCINTYRE, LEECH CK: A permanent change in brain function resulting from daily electrical stimulation. Exp. Neurol. (1969) 25:295-330.
226. JEFFERYS JGR, TRAUB RD: Electrophysiological substrates for focal epilepsies. Prog. Brain Res. (1998) 116:351-358. (Pubitemid 28526945)
227. MASUKAWA LM, HIGASHIMA M, HART GJ, SPENCER DD, O'CONNOR MJ: NMDA receptor activation during epileptiform responses in the dentate gyrus of epileptic patients. Brain Res. (1991) 562:176-180.
228. SHERWIN A, ROBITAILLE Y, QUESNEY F et al.: Excitatory amino acids are elevated in human epileptic cerebral cortex. Neurology (1988) 38:920-923.
229. JANJUA NA, ITANO T, KUGOH T et al.: Familial increase in plasma glutamic acid in epilepsy. Epilepsy Res. (1992) 11:37-44.
230. WILSON CL, MAIDMENT NT, SHOMER MH et al.: Comparison of seizure related amino acid release in human epileptic hippocampus versus a chronic, kainate rat model of hippocampal epilepsy. Epilepsy Res. (1996) 265:245-254. (Pubitemid 26420746)
231. DURING NC, SPENCER DD: Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet (1993) 341:1607-1610. (Pubitemid 23175242)
232. LOTHMAN WE, BENNETT JP, PERLIN JB: Alterations in neurotransmitter amino acids in hippocampal kindled seizures. Epilepsy Res. (1987) 1:313-320. (Pubitemid 17160941)
233. JANJUA NA, KABUTO H, MORI A: Increased plasma glutamic acid in a genetic model of epilepsy. Neurochem. Res. (1992) 17:293-296.
234. ZHANG WQ, HUDSON PM, SOBOTKA TJ, HONG JS, TILSON HA: Extracellular concentrations of amino acid transmitters in ventral hippocampus during and after the development of kindling. Brain. Res. (1991) 540:315-318.
235. OBRENOVITCH TP, URENJAK J, ZILKHA E: Evidence disputing the link between seizure activity and high extracellular glutamate. J. Neurochem. (1996) 66:2446-2454. (Pubitemid 26159080)
236. LEACH MJ, O'DONNELL RA, COLLINS KJ, MARDEN CM, MILLER AA: Effect of cortical kindling on [3H]D-aspartate uptake and glutamate metabolism in rats. Epilepsy Res. (1987) 1:145-148. (Pubitemid 18048287)
237. O'CONNOR ER, PIZZONIA JH, SPENCER DD, DE LANEROLLE NC: Glutamate, aspartate, and GABA transport in astrocytes cultured from human epileptic foci. Epilepsia (1996) 37(Suppl. 5):51.
238. SIMANTOV R, CRISPINO M, HOE W et al.: Changes in expression of neuronal and glial glutamate transporters in rat hippocampus following kainateinduced seizure activity. Mol. Brain. Res. (1999) 65:112-123. (Pubitemid 29138684)
239. YASHOR D, ZHU Z, ARMSTRONG DL et al.: Selective loss of EAAT2, a glial transporter, in CA1 and CA4 hippocampal subfields in Ammon's Horn Sclerosis. Epilesia (1996) 37(Suppl. 5):213.
240. TESSLER S, DANBOLT NC, FAULL RLM, STORM-MATHISEN J, EMSON PC: Expression of the glutamate transporters in human temporal lobe epilepsy. J. Neurosci. (1999) 88:1083-1091. (Pubitemid 28546991)
241. AKBAR MT, TORP R, DANBOLT NC et al.: Expression of glial glutamate transporters GLT-1 and GLAST is unchanged in the hippocampus in fully kindled rats. Neuroscience (1997) 78:351-359. (Pubitemid 27170327)
242. MILLER HP, LEVEY AI, ROTHSTEIN JD et al.: Alterations in glutamate transporter protein levels in kindlinginduced epilepsy. J. Neurochem. (1997) 68:1564-1570. (Pubitemid 27133064)
243. SUTHERLAND ML, DELANEY TA, NOEBELS JL: Subtypespecific downregulation of glutamate transporter gene expression in three models of temporal lobe epilepsy. Epilepsia (1997) 38(Suppl. 8):5-6.
244. NONAKA M, KOHMURA E, YAMASHITA T et al.: Increased transcription of glutamate-aspartate transporter (GLAST/GluT-1) mRNA following kainic acid-induced limbic seizure. Brain Res. (1998) 55:54-60. (Pubitemid 28236591)
245. ROGAWSKI MA: Excitatory amino acids and seizures. In: CNS Neurotransmitters and Neuromodulators: Glutamate. Stone TW (Ed.), CRC Press, Boca Raton, Florida, USA (1995):219-237.
246. COYLE JT: The glutamatergic dysfunction hypothesis for schizophrenia. Harvard Rev. Psychiatry (1996) 3:241-253. (Pubitemid 26058365)
247. GOFF DC, WINE L: Glutamate in schizophrenia: clinical and research implications. Schiz. Res. (1997) 27:157-168. (Pubitemid 27512852)
248. ARNOLD SE: Schizophrenia. In: Cell Death and Diseases of the Nervous System. Koliatsos VE, Ratan R. (Eds.), Humana Press, Totowa, NJ, USA (1999):527-541.
249. TSAI G, PASSANI LA, SLUSHER BS et al.: Abnormal excitatory neurotransmitter metabolism in schizophrenic brains. Arch. Gen. Psychiatry (1995) 52:829-836.
250. ISHIMARU M, KURAMAJI A, TORU M: Increases in strychnine-insensitive glycine binding sites in cerebral cortex of chronic schizophrenics: evidence for glutamate hypothesis. Biol. Psychiatry (1996) 35:84-95.
251. KERKERIAN L, DUSTICIER N, NIEOULLON A: Modulatory effect of dopamine on high-affinity glutamate uptake in the rat striatum. J. Neurochem. (1987) 48:1301-1306. (Pubitemid 18001357)
252. MAURA G, GIARDI A, RAITERI M: Release-regulating D-2 dopamine receptors are located on striatal glutamatergic nerve terminals. J. Pharmacol. Exp. Ther. (1988) 247:680-684.
253. JEDEMA HP, MOGHADDAM B: Glutamatergic control of dopamine release during stress in the rat prefrontal cortex. J. Neurochem. (1994) 63:785-788. (Pubitemid 24233719)
254. MOGHADDAM B, ADAMS BW: Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science (1998) 281:1349-1352. (Pubitemid 28406826)
255. BACHUS SE, HYDE TM, SHANNON WEICKERT C, SHASHIDHARAN P, HERMAN MM, KLEINMAN JE: Reduced level of excitatory amino acid transporter 3 mRNA in hippocampus of schizophrenics. Soc. Neurosci. Abstr. (1996) 22:1680.
256. OHNUMA T, AUGOOD SJ, ARAI H, MCKENNA PJ, EMSON PC: Expression of the human excitatory amino acid transporter 2 and metabotropic glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and patients with schizophrenia. Brain Res. Mol. Brain Res. (1998) 56:207-217. (Pubitemid 28271678)
257. LIN CLG, JACKSON M, JIN L et al.: Identification and characterization of purkinje cell-specific glutamate transporter EAAT4 associated proteins (GTRAP4). Soc. Neurosi. Abstr. (1998) 24:2068.
258. ORLOV I, LIN CLG, SON W et al.: GTRAP3: identification and characterization of a neuronal transporter EAAC1-associated protein. Soc. Neurosi. Abstr. (1998) 24:2068.