N-acetylaspartylglutamate: The most abundant peptide neurotransmitter in the mammalian central nervous system

Journal of Neurochemistry

Volumn 75, Issue 2, 2000, Pages 443-452

  Neale, Joseph H ^a   Bzdega, Tomasz ^a   Wroblewska, Barbara ^a  

^a GEORGETOWN UNIVERSITY   (United States)

Author keywords

Excitotoxicity; Metabotropic glutamate receptor agonist; N Acetylaspartylglutamate; Peptide neurotransmitter

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; CALCIUM; CYCLIC AMP; METABOTROPIC RECEPTOR; N ACETYLASPARTYLGLUTAMIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR;

ACTION POTENTIAL; CALCIUM CONDUCTANCE; CENTRAL NERVOUS SYSTEM; ENZYME ACTIVITY; HUMAN; HYDROLYSIS; LONG TERM POTENTIATION; NEUROTRANSMISSION; NONHUMAN; PRIORITY JOURNAL; RECEPTOR UPREGULATION; REVIEW; SYNAPSE VESICLE;

ANIMALS; CENTRAL NERVOUS SYSTEM; DIPEPTIDES; HUMANS; MAMMALS; NEURONS; NEUROPEPTIDES; NEUROTRANSMITTER AGENTS;

MAMMALIA;

EID: 0033943840     PISSN: 00223042     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1471-4159.2000.0750443.x     Document Type: Review

References (110)

1. Anderson K. J., Monaghan D. T., Cangro C. B., Namboodiri M. A. A., Neale J. H., and Cotman C. W. (1986) Localization of N-acetylaspartylglutamate-like immunoreactivity in selected areas of rat brain. Neurosci. Lett. 72, 14-20.
2. Anderson K. J., Borja M. A., Cotman C. W., Moffett J. R., Namboodiri M. A. A., and Neale J. H. (1987) N-Acetylaspartylglutamate identified in the rat retinal ganglion cells and their projections in the brain. Brain Res. 73, 172-177.
3. Berger U. V. and Schwab M. E. (1996) N-Acetylated alpha-linked acidic peptidase may be involved in axon-Schwann cell signaling. J. Neurocytol. 25, 499-512.
4. Berger U. V., Carter R. E., McKee M., and Coyle J. T. (1995) N-Acetylated alpha-linked acidic peptidase is expressed by non-myelinating Schwann cells in the peripheral nervous system. J. Neurocytol. 24, 99-109.
5. Berger U. V., Luthi-Carter R., Passani L. A., Elkabes S., Black I., Konradi C., and Coyle J. T. (1999) Glutamate carboxypeptidase II is expressed by astrocytes in the adult rat nervous system. J. Comp. Neurol. 415, 52-64.
6. Bernstein J., Fisher R. S., Zaczek R., and Coyle J. T. (1985) Dipeptides of glutamate and aspartate may be endogenous neuroexcitants in the rat hippocampal slice. J. Neurosci. 5, 1429-1433.
7. Bischofberger J. and Schild D. (1996) Glutamate and N-acetylaspartylglutamate block HVA calcium currents in frog olfactory bulb interneurons via a mGluR2/3-like receptor. J. Neurophysiol. 76, 2089-2092.
8. Blakely R. D., Ory-Lavollee L., Grzanna R., Koller K. J., and Coyle J. T. (1987) Selective immunocytochemical staining of mitral cells in rat olfactory bulb with affinity purified antibodies against N-acetyl-aspartyl-glutamate. Brain Res. 402, 373-378.
9. 3H]glutamate binding sites. Eur. J. Pharmacol. 151, 419-426.
10. Blakely R. D., Robinson M. B., Thompson R. C., and Coyle J. T. (1988b) Hydrolysis of the brain dipeptide N-acetyl-L-aspartyl-L-glutamate: subcellular and regional distribution, ontogeny, and the effects of lesions on N-acetylated α-linked acidic dipeptidase activity. J. Neurochem. 50, 1200-1209.
11. Brovia V., Costa A., and Barbeito L. (1996) N-Acetylsuccinimidylglutamate, a cyclic imide form of the peptide N-acetylaspartylglutamate, is present in low micromolar concentrations in murine and bovine CNS. J. Neurochem. 67, 382-388.
12. Bruno V., Wroblewska B., Wroblewski J. T., Fiore L., and Nicoletti F. (1998a) Neuroprotective activity of N-acetylaspartylglutamate in cultured cortical cells. Neuroscience 85, 751-757.
13. Bruno V., Battaglia G., Casabona G., Copani A., Caciagli F., and Nicoletti F. (1998b) Neuroprotection by glial metabotropic glutamate receptors is mediated by transforming growth factor-beta. J. Neurosci. 18, 9594-9600.
14. Burlina A. P., Skaper S. D., Mazza M. R., Ferrari V., Leon A., and Burlina A. B. (1994) N-Acetylaspartylglutamate selectively inhibits neuronal responses to N-methyl-D-aspartic acid in vitro. J. Neurochem. 63, 1174-1177.
15. Bzdega T., Turi T., Wroblewska B., She D., Chung H. S., Kim H., and Neale J. H. (1997) Molecular cloning of a peptidase against N-acetylaspartylglutamate (NAAG) from a rat hippocampal cDNA library. J. Neurochem. 69, 2270-2278.
16. Cangro C. B., Namboodiri M. A. A., Sklar L. A., Corigliano-Murphy A., and Neale J. H. (1987) Immunohistochemistry and biosynthesis of N-acetylaspartylglutamate in spinal sensory ganglia. J. Neurochem. 49, 1579-1588.
17. Carter R. E., Feldman A. R., and Coyle J. T. (1996) Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase. Proc. Natl. Acad. Sci. USA 93, 749-753.
18. 3H]-DCG IV) binding to metabotropic mGluR2 receptor-transfected cell membranes. Br. J. Pharmacol. 123, 497-504.
19. Cassidy M. and Neale J. H. (1993a) N-Acetylaspartylglutamate catabolism is achieved by an enzyme on the cell surface of neurons and glia. Neuropeptides 24, 271-278.
20. Cassidy M. and Neale J. H. (1993b) Localization and transport of N-acetylaspartylglutamate in cells of whole murine brain in primary culture. J. Neurochem. 60, 1631-1638.
21. Chavis P., Shinozaki H., Bockaert J., and Fagni L. (1994) The metabo-tropic glutamate receptor types 2/3 inhibit L-type calcium channels via a pertussis toxin-sensitive G-protein in cultured cerebellar granule cells. J. Neurosci. 14, 7067-7076.
22. Corse A. M., Thomas A. G., Coccia C. F., Rothstein J. D., and Slusher B. S. (1997) NAALADase inhibition protects motor neurons against chronic glutamate toxicity. Soc. Neurosci. Abstr. 23, 2301.
23. Curatelo A., D'Archangelo P., Lino A., and Brancati A. (1965) Distribution of N-acetyl-aspartic and N-acetyl-aspartyl-glutamic acids in nervous tissue. J. Neurochem. 12, 339-342.
24. ffrench-Mullen J. M. H., Koller K., Zaczek R., Coyle J. T., Hori N., and Carpenter D. O. (1985) N-Acetylaspartylglutamate: possible role as the neurotransmitter of the lateral olfactory tract. Proc. Natl. Acad. Sci. USA 82, 3897-3900.
25. Forloni G., Grzanna R., Blakely R. D., and Coyle J. T. (1987) Co-localization of N-acetylaspartylglutamate in central cholinergic, noradrenergic and serotonergic neurons. Synapse 1, 455-460.
26. Frondoza C. G., Logan S., Forloni G., and Coyle J. T. (1990) Production and characterization of monoclonal antibodies to N-acetyl-aspartyl-glutamate. J. Histochem. Cytochem. 38, 493-502.
27. Fuhrman S., Palkovits M., Cassidy M., and Neale J. H. (1994) The regional distribution of N-acetylaspartylglutamate (NAAG) and peptidase activity against NAAG in the rat nervous system. J. Neurochem. 62, 275-281.
28. Galli T., Godeheu G., Artaud F., Desce J. M., Pittaluga A., Barbeito L., Glowinski J., and Cheramy A. (1991) Specific role of N-acetyl-aspartyl-glutamate in the in vivo regulation of dopamine release from dendrites and nerve terminals of nigrostriatal dopaminergic neurons in the cat. Neuroscience 42, 19-28.
29. A α6 subunit in cerebellar granule cells. J. Neurochem. 69, 2326-2336.
30. Gingras R., Richard C., El-Alfy M., Morales C. R., Potier M., and Pshezhetsky A. V. (1999) Purification, cDNA cloning, and expression of a new human blood plasma glutamate carboxypeptidase homologous to N-acetyl-aspartyl-α-glutamate carboxypeptidase/prostate-specific membrane antigen. J. Biol. Chem. 274, 11742-11750.
31. Grunze H. C. R., Rainnie D. G., Hasselmo M. E., Barkai E., Hearn E. F., McCarley R. W., and Greene R. W. (1996) NMDA-dependent modulation of CA1 local circuit inhibition. J. Neurosci. 16, 2034-2043.
32. Guarda A. S., Robinson M. B., Ory-Lavollee L., Forloni G. L., Blakely R. D., and Coyle J. T. (1988) Quantitation of N-acetyl-aspartyl-glutamate in microdissected rat brain nuclei and peripheral tissues: findings with a novel liquid phase radioimmunoassay. Brain Res. 427, 223-231.
33. Halsted C. H., Ling E., Luthi-Carter R., Villanueva J. A., Gardner J. M., and Coyle J. T. (1998) Folylpoly-γ-glutamate carboxypeptidase from pig jejunum. Molecular characterization and relation to glutamate carboxypeptidase II. J. Biol. Chem. 273, 20417-20424.
34. Hess S. D., Pasieczny R., Rao S. P., Jachec C., Varney M. V., and Johnson E. C. (1999) Activity of N-acetylaspartylglutamate at human recombinant glutamate receptors. Soc. Neurosci. Abstr. 25, 975.
35. Huang L., Rowan M. J., and Anwyl R. (1999) Induction of long-lasting depression by (+)-alpha-methyl-4-carboxyphenylglycine and the other group II mGlu receptor ligands in the dentate gyrus of the hippocampus in vitro. Eur. J. Pharmacol. 366, 151-158.
36. Ishida M., Saitoh T., Shimamoto K., Ohfune Y., and Shinozaki H. (1993) A novel metabotropic glutamate receptor agonist: marked depression of monosynaptic excitation in the newborn rat isolated spinal cord. Br. J. Pharmacol. 109, 1169-1177.
37. Israeli R. S., Powell C. T., Fair W. R., and Heston W. D. W. (1993) Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen. Cancer Res. 53, 227-230.
38. Jackson P. F., Cole D. C., Slusher B. S., Stetz S. L., Ross L. E., Donzanti B. A., and Trainor D. A. (1996) Design, synthesis, and biological activity of a potent inhibitor of the neuropeptidase N-acetylated α-linked acidic dipeptidase. J. Med. Chem. 39, 619-622.
39. Joëls M., Van Veldhuizen M., Urban I. J. A., and DeKloet E. R. (1987) N-Acetylaspartylglutamate: binding studies and excitatory action in the dorsolateral septum of rats. Brain Res. 403, 192-197.
40. Jones H. S. and Sillito A. M. (1992) The action of the putative neurotransmitters N-acetylaspartylglutamate and L-homocysteate in cat dorsal lateral geniculate nucleus. J. Neurophvsiol. 68, 663-672.
41. Kamiya H., Shinozaki H., and Yamamoto C. (1996) Activation of metabotropic glutamate receptor type 2/3 suppresses transmission at rat hippocampal mossy fibre synapses. J. Physiol. (Lond.) 493, 447-455.
42. 2+ in vitro. Neuroreport 5, 1063-1068.
43. 3H] L-glutamate receptors. Eur. J. Pharmacol. 98, 193-199.
44. 3H]-N-acetylaspartylglutamate to rat brain membranes. J. Neurosci. 5, 2882-2888.
45. Koller K. J., Zaczek R., and Coyle J. T. (1984) N-Acetyl-aspartyl-glutamate: regional levels in rat brain and the effects of brain lesions as determined by a new HPLC method. J. Neurochem. 43, 1136-1142.
46. Kowalski M. M., Cassidy M., Namboodiri M. A., and Neale J. H. (1987) Cellular localization of N-acetylaspartylglutamate in amphibian retina and spinal sensory ganglia. Brain Res. 406, 397-401.
47. Lea P. M. IV, Wroblewska B., Neale J. H., and Sarvey J. M. (1999) β-NAAG rescues LTP from blockade by NAAG in rat dentate gyrus via mGluR3 receptor. Soc. Neurosci. Abstr. 25, 1231.
48. Luthi-Carter R., Berger U. V., Barczak A. K., and Coyle J. T. (1998) Isolation and expression of rat brain cDNA encoding glutamate carboxypeptidase II. Proc. Natl. Acad. Sci. USA 95, 3215-3220.
49. Macek T. A., Winder D. G., Gereau R. W., Ladd C. O., and Conn J. P. (1996) Differential involvement of group II and group III mGluRs as autoreceptors at lateral and medial perforant path synapses. J. Neurophysiol. 76, 3798-3806.
50. Meyerhoff J. L., Koller K. J., Walczak D. D., and Coyle J. T. (1985) Regional brain levels of N-acetyl-aspartyl-glutamate: the effect of kindled seizures. Brain Res. 346, 392-396.
51. Meyerhoff J. L., Robinson M. B., Bixler M. A., Richards S. S., and Coyle J. T. (1989) Seizures decrease regional enzymatic hydrolysis of N-acetylaspartylglutamate in rat brain. Brain Res. 505, 130-134.
52. Meyerhoff J. L., Robinson M. B., Koller K. J., Bixler M. A., and Coyle J. T. (1992) Kindling increases brain levels of NAAG and seizures reduce activity of NAAG-hydrolyzing enzyme, NAALADase. Epilepsy Res. Suppl. 8, 297-305.
53. Miyake M., Kikimoto Y., and Sorimachi M. (1981) A gas chromatographic method for the determination of N-acetyl-L-aspartic acid, N-acetyl-α-aspartylglutamic acid and β-citryl-L-glutamic acid and their distributions in brain and other organs of various species of animals. J. Neurochem. 36, 804-810.
54. Miyamoto M., Kakimoto Y., and Sano I. (1966) Identification of N-acetyl-aspartyl-glutamic acid in the bovine brain. J. Neurochem. 13, 999-1003.
55. Moffett J. R. and Namboodiri M. A. A. (1995) Differential distribution of N-acetylaspartylglutamate and N-acetylaspartate immunoreactivities in rat forebrain. J. Neurocytol. 24, 409-433.
56. Moffett J. R., Palkovits M., Namboodiri M. A. A., and Neale J. H. (1994) Comparative distribution of N-acetylaspartylglutamate and GAD67 in the cerebellum and precerebellar nuclei of the rat utilizing enhanced carbodiimide fixation and immunohistochemistry. J. Comp. Neurol. 347, 598-618.
57. Mori-Okamoto J., Okamoto K., and Sekiguchi M. (1987) Electrophysiological and pharmacological actions of N-acetylaspartylglutamate intracellularly studied in cultured chick cerebellar neurons. Brain Res. 401, 60-67.
58. Nan F., Bzdega T., Pshenichkin S., Wroblewski J. T., Wroblewska B., Neale J. H., and Kozikowski A. P. (2000) Dual function-related ligands: discovery of a novel, potent inhibitor of glutamate carboxypeptidase II possessing mGluR3 agonist activity. J. Med. Chem. 43, 772-774.
59. Ohishi H., Ogawa-Meguro R., Shigemoto R., Kaneko T., Nakanishi S., and Mizuno N. (1994) Immunohistochemical localization of metabotropic glutamate receptors, mGluR2 and mGluR3, in rat cerebellar cortex. Neuron 13, 55-66.
60. Orlando L. R., Luthi-Carter R., Standaert D. G., Coyle J. T., Penney J. B. Jr., and Young A. B. (1997) N-Acetylaspartylglutamate (NAAG) protects against rat striatal quinolinic acid lesions in vivo. Neurosci. Lett. 236, 91-94.
61. Pangalos M. N., Neefs J.-M., Somers M., Verhasselt P., Bekkers M., van der Helm L., Fraiponts E., Ashton D., and Gordon R. D. (1999) Isolation and expression of novel human glutamate carboxypeptidase with N-acetylated α-linked acidic dipeptidase and dipeptidyl peptidase IV activity. J. Biol. Chem. 274, 8470-8483.
62. Passani L. A., Vonsattel J. P., and Coyle J. T. (1997a) Distribution of N-acetylaspartylglutamate immunoreactivity in human brain and its alteration in neurodegenerative disease. Brain Res. 772, 9-22.
63. Passani L. A., Vonsattel J. P., Carter R. E., and Coyle J. T. (1997b) N-Acetylaspartylglutamate, N-acetylaspartate, and N-acetylated alpha-linked acidic dipeptidase in human brain and their alteration in Huntington and Alzheimer's diseases. Mol. Chem. Neuropathol. 31, 97-118.
64. Passani L., Elkabes S., and Coyle J. T. (1998) Evidence of the presence of N-acetylaspartylglutamate in cultured oligodendrocytes and LPS activated microglia. Brain Res. 794, 143-145.
65. Petralia R. S., Wang Y. X., Zhao H. M., and Wenthold R. J. (1996) Ionotropic and metabotropic glutamate receptors show unique postsynaptic, presynaptic, and glial localization in the dorsal cochlear nucleus. J. Comp. Neurol. 372, 356-383.
66. Pittaluga A., Barbeito L., Serval V., Godeheu G., Artaud F., Glowinski J., and Cheramy A. (1988) Depolarization-evoked release of N-acetyl-L-aspartyl-L-glutamate from rat brain synaptosomes. Eur. J. Pharmacol. 158, 263-266.
67. 3H]-norepinephrine release from rat hippocampal slices. J. Pharmacol. Exp. Ther. 266, 796-803.
68. Renno W. M., Lee J. H., and Beitz A. J. (1997) Light and electron microscopic immunohistochemical localization of N-acetylaspartylglutamate (NAAG) in the olivocerebellar pathway of the rat. Synapse 26, 140-154.
69. Riveros N. and Orrego F. (1984) A study of possible excitatory effects of N-acetylaspartylglutamate in different in vivo and in vitro brain preparations. Brain Res. 299, 393-395.
70. Robinson M. B., Blakely R. D., Couto R., and Coyle J. T. (1987) Hydrolysis of the brain dipeptide N-acetyl-L-aspartyl-L-glutamate. Identification and characterization of a novel N-acelylated α-linked acidic dipeptidase activity from rat brain. J. Biol. Chem. 262, 14498-14506.
71. Sah P., Hestrin S., and Nicoll R. A. (1989) Tonic activity of NMDA receptors by ambient glutamate enhances excitability of neurons. Science 246, 815-818.
72. Sayer R. J., Schwindt P. C., and Crill W. E. (1992) Metabotropic glutamate receptor-mediated suppression of L-type calcium current in acutely isolated neocortical neurons. J. Neurophysiol. 68, 833-842.
73. 3H]GABA release by metabotropic glutamate receptors, in primary rat cortical cultures. Brain Res. 782, 91-104.
74. 3H]-acetylaspartylglutamate binding in rat brain: selective inhibition of phosphoinositide hydrolysis by 2-amino-3-phosphonopropionate. J. Neurochem. 53, 273-278.
75. Schoepp D. D., Jane D. E., and Monn J. A. (1999) Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacology 38, 1431-1476.
76. Sekiguchi M., Okamoto K., and Sakai Y. (1987) Excitatory action of N-acetylaspartylglutamate on Purkinje cells in guinea pig cerebellar slices: an intrasomatic study. Brain Res. 423, 23-33.
77. Sekiguchi M., Okamoto K., and Sakai Y. (1989a) Low concentration N-acetylaspartylglutamate suppresses the climbing fiber response of Purkinje cells in guinea pig cerebellar slices and the responses to excitatory amino acids of Xenopus laevis oocytes injected with cerebellar mRNA. Brain Res. 482, 87-96.
78. 3H]NAAG in guinea pig cerebellar slices. Brain Res. 482, 78-86.
79. Sekiguchi M., Wada K., and Wenthold R. J. (1992) N-Acetylaspartylglutamate acts as an agonist upon homomeric NMDA receptor (NMDAR1) expressed in Xenopus oocytes. FEBS Lett. 311, 285-289.
80. Serval V., Barbeito L., Pittaluga A., Cheramy A., Lavielle S., and Glowinski J. (1990) Competitive inhibition of N-acetylated-α-linked acidic dipeptidase activity by N-acetyl-L-aspartyl-β-linked L-glutamate. J. Neurochem. 55, 39-46.
81. Shigemoto R., Kinoshita A., Wada E., Nomura S., Ohishi H., Takada M., Flor P. J., Neki A., Abe T., Nakanishi S., and Mizuno N. (1997) Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. J. Neurosci. 17, 7503-7522.
82. Slusher B. S., Robinson M. B., Tsai G., Simmons M. L., Richards S. S., and Coyle J. T. (1990) Rat brain N-acetylated α-linked acidic dipeptidase activity. Purification and immunologic characterization. J. Biol. Chem. 265, 21297-21301.
83. Slusher B. S., Vornow J. J., Thomas A. G., Hum P. D., Harukuni I., Bhardwaj A., Traystman R. J., Robinson M. B., Britton P., MayLu X.-C., Tortella F. C., Wozniak K. M., Yudkoff M., Potter B. M., and Jackson P. F. (1999) Selective inhibition of NAALA-Dase, which converts NAAG to glutamate, reduces ischemic brain injury. Nat. Med. 5, 1396-1402.
84. Stauch-Slusher B. S., Tsai G., Yoo G., and Coyle J. T. (1992) Immunocytochemical localization of the N-acetyl-aspartyl-glutamate (NAAG) hydrolyzing enzyme N-acetylated α-linked acidic dipeptidase (NAALADase). J. Camp. Neurol. 315, 217-229.
85. Tieman S. B., Cangro C. B., and Neale J. H. (1987) N-Acetylaspartylglutamate immunoreactivity in neurons of the cat's visual system. Brain Res. 420, 188-193.
86. Tieman S. B., Butler K., and Neale J. H. (1988) N-Acetylaspartylglutamate: a neuropeptide in human visual system. JAMA 259, 2020.
87. Tieman S. B., Neale J. H., and Tieman D. G. (1991) N-Acetylaspartylglutamate immunoreactivity in neurons of the monkey's visual pathway. J. Comp. Neurol. 313, 45-64.
88. Trombley P. Q. and Westbrook G. L. (1990) Excitatory synaptic transmission in cultures of rat olfactory bulb. J. Neurophysiol. 64, 598-606.
89. 3H]acetylaspartylglutamate from the optic pathway. J. Neurochem. 51, 1956-1959.
90. Tsai G., Stauch B. L., Vornov J. J., Deshpande J. K., and Coyle J. T. (1990) Selective release of N-acetylaspartylglutamate from rat optic nerve terminals in vivo. Brain Res. 518, 313-316.
91. Tsai G. C., Stauch-Slusher B., Sim L., Hedreen J. C., Rothstein J. D., Kuncl R., and Coyle J. T. (1991) Reductions in acidic amino acids and N-acetylaspartylglutamate in amyotropic lateral sclerosis CNS. Brain Res. 556, 151-156.
92. Tsai G., Slusher B. S., Sim L., and Coyle J. T. (1993) Immunocytochemical distribution of N-acetylaspartylglutamate in the rat forebrain and glutamatergic pathway. J. Chem. Neuroanat. 6, 277-292.
93. Tsai G., Coyle J. T., Kleinman J. E., Baer L., Carter R., Slusher B. S., and Passani L. A. (1996) Abnormal excitatory neurotransmitter metabolism in schizophrenic brains. Arch. Gen. Psychiatry 52, 829-836.
94. Valivullah H. M., Lancaster J., Sweetnam P. M., and Neale J. H. (1994) Interactions between N-acetylaspartylglutamate and AMPA, kainate, and NMDA binding sites. J. Neurochem. 63, 1714-1719.
95. Vomov J. J., Wozniak K., Lu M., Jackson P., Tsukamoto T., Wang E., and Slusher B. (1999) Blockade of NAALADase: a novel neuroprotective strategy based on limiting glutamate and elevating NAAG. Ann. NY Acad. Sci. 890, 400-405.
96. Westbrook G., Mayer M. L., Namboodiri M. A. A., and Neale J. H. (1986) High concentrations of N-acetylaspartylglutamate (NAAG) selectively activate NMDA receptors on mouse spinal cord neurons in cell culture. J. Neurosci. 6, 3385-3392.
97. Whittemore E. R. and Koerner J. F. (1989) An explanation for the purported excitation of piriform cortical neurons by N-acetyl-L-aspartyl-L-glutamic acid (NAAG). Proc. Natl. Acad. Sci. USA 86, 9602-9605.
98. Williamson L. C. and Neale J. H. (1988a) Calcium-dependent release of N-acetylaspartylglutamate from retinal neurons upon depolarization. Brain Res. 475, 151-155.
99. Williamson L. C. and Neale J. H. (1988b) Ultrastructural localization of N-acetylaspartylglutamate in synaptic vesicles of retinal neurons. Brain Res. 456, 375-381.
100. 3H]acetylaspartylglutamate by the avian retina. J. Neurochem. 58, 2191-2199.
101. Williamson L. C., Eagles D. A., Brady M. J., Moffett J. R., Namboodiri M. A., and Neale J. H. (1991) Localization and synaptic release of N-acetylaspartylglutamate in the chick retina and optic tectum. Eur. J. Neurosci. 3, 441-451.
102. Wroblewska B., Wroblewski J. T., Saab O., and Neale J. H. (1993) N-Acetylaspartylglutamate inhibits forskolin-stimulated cyclic AMP levels via a metabotropic glutamate receptor in cultured cerebellar granule cells. J. Neurochem. 61, 943-948.
103. Wroblewska B., Wroblewski J. T., Pshenichkin S., Surin A., Sullivan S. E., and Neale J. H. (1997) N-Acetylaspartylglutamate selectively activates mGluR3 receptors in transfected cells. J. Neurochem. 69, 174-182.
104. Wroblewska B., Santi M. R., and Neale J. H. (1998) N-Acetylaspartylglutamate activates cyclic-AMP coupled metabotropic glutamate receptors in cerebellar astrocytes. Glia 24, 172-180.
105. Wroblewska B., Bzdega T., Neale J. H., Wroblewski J. T., Pshenichkin S., Nan F., and Kozikowski A. P. (1999) Synthetic analogs of NAAG are potent blockers of NAAG peptidase (glutamate carboxypeptidase II) in CHO cells. Soc. Neurosci. Abstr. 25, 975.
106. Yourick D. L., Koenig M. L., and Long J. B. (1998) N-Acetylaspartylglutamate (NAAG) attenuates hypoxia-and NMDA-induced cell death in spinal cord cultures. Soc. Neurosci. Abstr. 24, 463.
107. Zaczek R., Koller K., Cotter R., Heller D., and Coyle J. T. (1983) N-Acetylaspartylglutamate: an endogenous peptide with high affinity for a brain "glutamate" receptor. Proc. Natl. Acad. Sci. USA 80, 1116-1119.
108. 3H]-GABA release in cultured rat cortical neurons. Soc. Neurosci. Abstr. (in press).
109. Zollinger M., Amsler U., Do K. Q., Streit P., and Cuénod M. (1988) Release of N-acetylaspartylglutamate on depolarization of rat brain slices. J. Neurochem. 51, 1919-1923.
110. Zollinger M., Brauchli-Theotokis J., Gutteck-Amsler U., Do K. Q., Streit P., and Cuénod M. (1994) Release of N-acetylaspartylglutamate from slices of rat cerebellum, striatum, and spinal cord, and the effect of climbing fiber deprivation. J. Neurochem. 63, 1133-1142.