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Br J Pharmacol
2005 Jun 01;1454:449-59. doi: 10.1038/sj.bjp.0706199.
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D-aspartate and NMDA, but not L-aspartate, block AMPA receptors in rat hippocampal neurons.
Gong XQ
,
Frandsen A
,
Lu WY
,
Wan Y
,
Zabek RL
,
Pickering DS
,
Bai D
.
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1 The amino acid, D-aspartate, exists in the mammalian brain and is an agonist at the N-methyl-D-aspartate (NMDA) subtype of ionotropic glutamate receptors. Here, for the first time, we studied the actions of D-aspartate on alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate receptors (AMPARs) in acutely isolated rat hippocampal neurons. 2 In the presence of the NMDA receptor channel blocker, MK801, D-aspartate inhibited kainate-induced AMPAR current in hippocampal neurons. The inhibitory action of D-aspartate on kainate-induced AMPAR current was concentration-dependent and was voltage-independent in the tested voltage range (-80 to +60 mV). 3 The estimated EC50 of the L-glutamate-induced AMPAR current was increased in the presence of D-aspartate, while the estimated maximum L-glutamate-induced AMPAR current was not changed. D-aspartate concentration-dependently shifted the dose-response curve of kainate to the right. Schild plot analysis indicated that D-aspartate acts competitively to block AMPARs. The K(b) for D-aspartate was estimated to be 0.93 mM. 4 D-aspartate also blocked L-glutamate-induced current in Xenopus laevis oocytes that expressed recombinant homomeric AMPARs. 5 NMDA possessed similar inhibitory action on AMPARs. However, L-aspartate had little inhibitory action on AMPARs. 6 D-Aspartate, but not L-aspartate, was found to reduce the amplitude of miniature excitatory postsynaptic current in cultured hippocampal neurons. 7 Our data are consistent with a model in which D-aspartate directly competes with kainate and L-glutamate in binding to the agonist binding site of AMPARs. The prevalence of D-aspartate in the brain suggests a possible role of D-aspartate in modulating AMPAR-mediated fast excitatory synaptic transmission.
Albus,
Tetanus toxin inhibits the evoked outflow of an inhibitory (GABA) and an excitatory (D-aspartate) amino acid from particulate brain cortex.
1983, Pubmed
Albus,
Tetanus toxin inhibits the evoked outflow of an inhibitory (GABA) and an excitatory (D-aspartate) amino acid from particulate brain cortex.
1983,
Pubmed
Bai,
Non-ionotropic cross-talk between AMPA and NMDA receptors in rodent hippocampal neurones.
2002,
Pubmed
Bliss,
A synaptic model of memory: long-term potentiation in the hippocampus.
1993,
Pubmed
Brackley,
Are chimeric kainate/N-methyl-D-aspartate receptors expressed in Xenopus oocytes from mammalian and amphibian RNA?
1993,
Pubmed
,
Xenbase
Coquelle,
Agonist discrimination between AMPA receptor subtypes.
2000,
Pubmed
,
Xenbase
D'Aniello,
Occurrence of D-aspartic acid and N-methyl-D-aspartic acid in rat neuroendocrine tissues and their role in the modulation of luteinizing hormone and growth hormone release.
2000,
Pubmed
D'Aniello,
Involvement of D-aspartic acid in the synthesis of testosterone in rat testes.
1996,
Pubmed
Davies,
D-aspartate oxidase activity in extracts of mammalian central nervous tissue.
1975,
Pubmed
Dingledine,
The glutamate receptor ion channels.
1999,
Pubmed
Dunlop,
The presence of free D-aspartic acid in rodents and man.
1986,
Pubmed
Fisher,
Free D-amino acids in human cerebrospinal fluid of Alzheimer disease, multiple sclerosis, and healthy control subjects.
1994,
Pubmed
Fleck,
Synaptosomal and vesicular accumulation of L-glutamate, L-aspartate and D-aspartate.
2001,
Pubmed
Fleck,
Aspartate and glutamate mediate excitatory synaptic transmission in area CA1 of the hippocampus.
1993,
Pubmed
Gundersen,
Quantification of excitatory amino acid uptake at intact glutamatergic synapses by immunocytochemistry of exogenous D-aspartate.
1995,
Pubmed
Hamase,
Regional distribution and postnatal changes of D-amino acids in rat brain.
1997,
Pubmed
Hashimoto,
Embryonic development and postnatal changes in free D-aspartate and D-serine in the human prefrontal cortex.
1993,
Pubmed
Hashimoto,
Anatomical distribution and postnatal changes in endogenous free D-aspartate and D-serine in rat brain and periphery.
1995,
Pubmed
Huettner,
Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels.
1988,
Pubmed
Karschin,
The interaction of agonists and noncompetitive antagonists at the excitatory amino acid receptors in rat retinal ganglion cells in vitro.
1988,
Pubmed
Kera,
Presence of free D-glutamate and D-aspartate in rat tissues.
1995,
Pubmed
Kiskin,
Cross-desensitization Reveals Pharmacological Specificity of Excitatory Amino Acid Receptors in Isolated Hippocampal Neurons.
1990,
Pubmed
Lei,
Positive allosteric modulators of AMPA receptors reduce proton-induced receptor desensitization in rat hippocampal neurons.
2001,
Pubmed
Lerma,
N-methyl-D-aspartate activates different channels than do kainate and quisqualate.
1989,
Pubmed
,
Xenbase
Lerma,
mRNA from NCB-20 cells encodes the N-methyl-D-aspartate/phencyclidine receptor: a Xenopus oocyte expression study.
1989,
Pubmed
,
Xenbase
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
MacDonald,
Actions of ketamine, phencyclidine and MK-801 on NMDA receptor currents in cultured mouse hippocampal neurones.
1991,
Pubmed
Magazanik,
Competitive antagonism of recombinant AMPA/kainate receptors by N-methyl-D-aspartate and analogues.
1996,
Pubmed
,
Xenbase
Martire,
K(+)-Evoked [(3)H]D-aspartate release in rat spinal cord synaptosomes: modulation by neuropeptide Y and calcium channel antagonists.
2000,
Pubmed
Mayer,
The action of N-methyl-D-aspartic acid on mouse spinal neurones in culture.
1985,
Pubmed
Nakatsuka,
D-Aspartate is stored in secretory granules and released through a Ca(2+)-dependent pathway in a subset of rat pheochromocytoma PC12 cells.
2001,
Pubmed
Neidle,
Developmental changes in free D-aspartic acid in the chicken embryo and in the neonatal rat.
1990,
Pubmed
Palmer,
Comparison of the superfused efflux of preaccumulated D-[3H]aspartate and endogenous L-aspartate and L-glutamate from rat cerebrocortical minislices.
1994,
Pubmed
Patneau,
Structure-activity relationships for amino acid transmitter candidates acting at N-methyl-D-aspartate and quisqualate receptors.
1990,
Pubmed
Ruppersberg,
Studying block in cloned N-methyl-D-aspartate (NMDA) receptors.
1993,
Pubmed
Savage,
Characterization of electrically evoked [3H]-D-aspartate release from hippocampal slices.
2001,
Pubmed
Schell,
D-aspartate localizations imply neuronal and neuroendocrine roles.
1997,
Pubmed
Waagepetersen,
Comparison of effects of DL-threo-beta-benzyloxyaspartate (DL-TBOA) and L-trans-pyrrolidine-2,4-dicarboxylate (t-2,4-PDC) on uptake and release of [3h]D-aspartate in astrocytes and glutamatergic neurons.
2001,
Pubmed
Watkins,
Excitatory amino acid transmitters.
1981,
Pubmed
Yusko,
D-aspartate oxidase in mammalian brain and choroid plexus.
1973,
Pubmed
Zaar,
Cellular and subcellular distribution of D-aspartate oxidase in human and rat brain.
2002,
Pubmed