N-acetylated α-linked acidic dipeptidase converts N-acetylaspartylglutamate from a neuroprotectant to a neurotoxin

Journal of Pharmacology and Experimental Therapeutics

Volumn 295, Issue 1, 2000, Pages 16-22

  Thomas, Ajit G ^a   Vornov, James J ^a   Olkowski, Jennifer L ^a   Merion, Aviva T ^a   Slusher, Barbara S ^a  

^a GUILFORD PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (PHOSPHONOMETHYL) PENTANEDIONIC ACID; 6 CYANO 7 NITRO 2,3 QUINOXALINEDIONE; DIZOCILPINE; GAMMA GLUTAMYL HYDROLASE; GAMMA GLUTAMYL HYDROLASE 2; GLUTAMATE RECEPTOR AGONIST; N ACETYLASPARTYLGLUTAMIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NEUROPROTECTIVE AGENT; NEUROTOXIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG ACETYLATION; DRUG DISTRIBUTION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME MECHANISM; FETUS; HYDROLYSIS; INHIBITION KINETICS; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; RAT;

ANIMALS; BRAIN; CARBOXYPEPTIDASES; CELLS, CULTURED; DIPEPTIDES; FEMALE; GLUTAMATE CARBOXYPEPTIDASE II; N-METHYLASPARTATE; NEUROPROTECTIVE AGENTS; PREGNANCY; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, N-METHYL-D-ASPARTATE;

EID: 0033810889     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (42)

1. Glutamate carboxypeptidase II is expressed by astrocytes in the adult rat nervous system
2. Dipeptides of glutamate and aspartate may be endogenous neuroexcitants in the rat hippocampal slice
3. Activation of class II or III metabotropic glutamate receptors protects cultured cortical neurons against excitotoxic degeneration
4. Neuroprotective activity of N-acetylaspartylglutamate in cultured cortical cells
5. The inhibitory mGluR agonist, S-4-carboxy-3-hydroxy-phenylglycine selectively attenuates NMDA neurotoxicity and oxygen-glucose deprivation-induced neuronal death
6. N-acetylaspartylglutamate catabolism is achieved by an enzyme on the cell surface of neurons and glia
7. Localization and transport of N-acetylaspartylglutamate in cells of whole murine brain in primary culture
8. MK-801 is neuroprotective in gerbils when administered during the post-ischaemic period
9. N-methyl-D-aspartate receptors mediate hypoxic neuronal injury in cortical culture
10. Role of a metabotropic glutamate receptor in synaptic modulation in the accessory olfactory bulb
11. Design, synthesis and biological activity of a potent inhibitor of the neuropeptidase N-acetylated alpha-linked acidic dipeptidase
12. N-acetylaspartylglutamate: Binding sites and excitatory action in the dorsolateral septum of rats
13. Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay
14. Protection against ischaemic neuronal damage by drugs acting on excitatory neurotransmission
15. N-Acetylaspartylglutamate: A transmitter candidate for the retinohypothalamic tract
16. Electrophysiological and pharmacological actions of N-acetylaspartylglutamate intracellularly studied in cultured chick cerebellar neurons
17. Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced
18. Distribution of N-acetylaspartylglutamate immunoreactivity in human brain and its alteration in neurodegenerative disease
19. Differential distribution of NAA and NAAG in human brain as determined by quantitative localized proton MRS
20. N-acetyl-aspartylglutamate modulation of N-methyl-D-aspartate-stimulated [3H]norepinephrine release from rat hippocampal slices
21. Hydrolysis of the brain dipeptide N-acetyl-L-aspartyl-L-glutamate. Identification and characterization of a novel N-acetylated alpha-linked acidic dipeptidase activity from rat brain
22. Inhibition of glutamate uptake with L-trans-pyrrolidine-2,4-dicarboxylate potentiates glutamate toxicity in primary hippocampal cultures
23. Glutamate and the pathophysiology of hypoxicischemic brain damage
24. Presynaptic receptors and the control of glutamate exocytosis
25. 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
26. N-acetylaspartylglutamate acts as an agonist upon homomeric NMDA receptor (NMDAR1) expressed in Xenopus oocytes
27. Competitive inhibition of N-acetylated-alpha-linked acidic dipeptidase activity by N-acetyl-L-aspartyl-beta-linked L-glutamate
28. Selective inhibition of NAALADase, which converts NAAG to glutamate, reduces ischemic brain injury
29. The effects of N-acetylated alpha-linked acidic dipeptidase (NAALADase) inhibitors on [3H]NAAG catabolism in vivo
30. Toxicity induced by a polyglutamated folate analog is attenuated by NAALADase inhibition
31. Calcium-dependent evoked release of N-[3H]acetylaspartylglutamate from the optic pathway
32. Immunocytochemical distribution of N-acetylaspartylglutamate in the rat forebrain and glutamatergic pathways
33. Selective release of N-acetylaspartylglutamate from rat optic nerve terminals in vivo
34. Interactions between N-acetylaspartylglutamate and AMPA, kainate, and NMDA binding sites
35. Toxic NMDA-receptor activation occurs during recovery in a tissue culture model of ischemia
36. Protective effects of extracellular acidosis and blockade of sodium/hydrogen ion exchange during recovery from metabolic inhibition in neuronal tissue culture
37. High concentrations of N-acetylaspartylglutamate (NAAG) selectively activate NMDA receptors on mouse spinal cord neurons in cell culture
38. An explanation for the purported excitation of piriform cortical neurons by N-acetyl-L-aspartyl-L-glutamic acid (NAAG)
39. Ultrastructural localization of N-acetylaspartylglutamate in synaptic vesicles of retinal neurons
40. Uptake, metabolism, and release of N-[3H]acetylaspartylglutamate by the avian retina
41. N-acetylaspartylglutamate selectively activates mGluR3 receptors in transfected cells
42. Release of N-acetylaspartylglutamate on depolarization of rat brain slices