Developmental and regional expression pattern of a novel NMDA receptor- like subunit (NMDAR-L) in the rodent brain

Sucher, Nikolaus J.; Akbarian, Schahram; Cl, Chi; Leclerc, CL; Awobuluyi, Marc; Deitcher, David L.; Wu, Mk; Yuan, JP; Jones, E.G.; Lipton, Stuart A.

doi:10.1523/jneurosci.15-10-06509.1995

Cited by 370 publications

(332 citation statements)

References 67 publications

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“…N R3 (NRL or Ch i-1 ) is expressed predominantly in the developing CNS. NR3 does not seem to form functional homomeric Glu-activated channels, but the co-expression of NR3 with NR1 plus NR2 subunits decreases any response magnitude [334][335][336][337] .…”

Section: ) Synaptic Plasticitymentioning

confidence: 99%

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Rousseaux

2008

J Toxicol Pathol

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Seventy years ago it was discovered that glutamate is abundant in the brain and that it plays a central role in brain metabolism. However, it took the scientific community a long time to realize that glutamate also acts as a neurotransmitter. Glutamate is an amino acid and brain tissue contains as much as 5 -15 mM glutamate per kg depending on the region, which is more than of any other amino acid. The main motivation for the ongoing research on glutamate is due to the role of glutamate in the signal transduction in the nervous systems of apparently all complex living organisms, including man. Glutamate is considered to be the major mediator of excitatory signals in the mammalian central nervous system and is involved in most aspects of normal brain function including cognition, memory and learning. In this review, the basic biology of the excitatory amino acids glutamate, glutamate receptors, GABA, and glycine will first be explored. In the second part of this review, the known pathophysiology and pathology will be described. (J Toxicol Pathol 2008; 21: 25-51)

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Section: ) Synaptic Plasticitymentioning

confidence: 99%

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Rousseaux

2008

J Toxicol Pathol

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“…A novel family of NMDA receptor subunits, consisting of NR3A and NR3B, has been described recently (Nishi et al, 2001;Sucher et al, 1995). NR3A has at least two splice variants (Sun et al, 1998).…”

Section: Pharmacology Of Glutamate Receptorsmentioning

confidence: 99%

“…NR3A has at least two splice variants (Sun et al, 1998). NR3 subunits form functional channels with NR1 , and, unlike other subunits, work in a dominant-negative fashion, i.e., they assemble with NR1 and suppress glutamate-induced currents (Nishi et al, 2001;Sucher et al, 1995).…”

Section: Pharmacology Of Glutamate Receptorsmentioning

confidence: 99%

“…However, in the light of NMDA receptor hypofunction, the expression of these receptor subtypes will be important to explore in schizophrenia. Levels of expression of the NR3A subunit are particularly interesting, as NR3A has been found in brain areas of significance for schizophrenia, such as cortical areas and the thalamus (Sucher et al, 1995). mGluRs are of interest for schizophrenia research as well.…”

Section: The Role Of Glutamate In Neurotoxicity-mentioning

confidence: 99%

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Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Konradi

Heckers

2003

Pharmacology & Therapeutics

288

165

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The glutamate system is involved in many aspects of neuronal synaptic strength and function during development and throughout life. Synapse formation in early brain development, synapse maintenance, and synaptic plasticity are all influenced by the glutamate system. The number of neurons and the number of their connections are determined by the activity of the glutamate system and its receptors. Malfunctions of the glutamate system affect neuroplasticity and can cause neuronal toxicity. In schizophrenia, many glutamate-regulated processes seem to be perturbed. Abnormal neuronal development, abnormal synaptic plasticity, and neurodegeneration have been proposed to be causal or contributing factors in schizophrenia. Interestingly, it seems that the glutamate system is dysregulated and that N-methyl-D-aspartate receptors operate at reduced activity. Here we discuss how the molecular aspects of glutamate malfunction can explain some of the neuropathology observed in schizophrenia, and how the available treatment intervenes through the glutamate system.

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“…Unexpectedly, however, these cysteines, C744 and C798, appear to be conserved in all ionotropic glutamate receptors when the sequences are aligned by overall homology. 42,57 Nonetheless, among the ionotropic glutamate receptors, only NMDA receptors are exquisitely sensitive to redox modulation and`NO' effects. 33,58 Inspection of the immediate amino acid neighbors of these cysteines revealed that the NR1 cysteines are distinguished from the cysteines conserved in the other ionotropic glutamate receptors in that they are Among candidates for regulation by S-nitrosylation that were identified by the database search were ion channels (NMDA receptor, voltage sensitive Na + channel, cyclic nucleotide-gated channel), transporters (Ca-ATPase, Ktransporter), receptors (inositol trisphosphate receptor, nerve growth factor receptor), enzymes (oxidoreductases, dehydrogenases, adenylate and guanylate cyclases, proteases, DNA topoisomerases, DNA and RNA polymerases, kinases, phosphatases), transcription factors (helix loop helix proteins, NF-kB, zinc finger proteins), small GTP binding proteins (rab, ras, sas, ypt), cell adhesion molecules (integrins, neural cell adhesion molecule), cell adhesion substrates (laminin, collagen), cyclins and coagulation factors (IXa, Xa, XIII).…”

Section: Proposed Consensus Motif For S-nitrosylationmentioning

confidence: 99%

Neuronal protection and destruction by NO

1999

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Nitric oxide (NO)-related species include different redox states of the NO group, which have recently been reported to exist endogenously in biological tissues including the brain. The importance of these different NO-related species is that their distinct chemical reactivities can influence the life and death of neurons in response to various insults. In the case of NO + equivalents (having one less electron than NO . ), the mechanism of reaction often involves Snitrosylation or transfer of the NO group to the sulfhydryl of a cysteine residue (or more properly to a thiolate anion) to form an RS-NO; further oxidation of critical thiols can possibly then form disulfide bonds from neighboring cysteine residues. We have mounted both physiological and chemical evidence that N-methyl-D-aspartate receptor (NMDAR) activity and caspase enzyme activity can be decreased by S-nitrosylation, as can other signaling molecules involved in neuronal apoptotic pathways, to afford neuroprotection. Over the past 5 years, beginning with our report on the NMDAR, evidence has accumulated that S-nitrosylation can regulate the biological activity of a great variety of proteins, in some ways akin to phosphorylation. Thus, this chemical reaction is gaining acceptance as a newly-recognized molecular switch to control protein function via reactive thiol groups, such as those encountered on the NMDAR and in the active site of caspases. One method of producing S-nitrosylation of the NMDAR and caspases is the administration of nitroglycerin, and nitroglycerin can be neuroprotective in acute focal ischemia/reperfusion models via mechanisms other than increasing cerebral blood flow. In contrast, NO . itself does not appear to react with thiol under physiological conditions. In fact, the favored reaction of NO . is with O 2 .7 (superoxide anion) to form ONOO 7 (peroxynitrite), which can lead to neurotoxicity. A third NO-related species with one added electron compared to NO . is nitroxyl anion (NO 7 ). NO 7 ± unlike NO . but reminiscent of NO + transfer ± reacts with critical thiol groups of the NMDA receptor to curtail excessive Ca 2+ influx and thus provide neuroprotection from excitotoxic insults.

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Developmental and regional expression pattern of a novel NMDA receptor- like subunit (NMDAR-L) in the rodent brain

Cited by 370 publications

References 67 publications

A Review of Glutamate Receptors I: Current Understanding of Their Biology

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Neuronal protection and destruction by NO

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