IV-methyl-D-aspartate receptors

Mesolimbic System/Reward System Metabolic Syndrome Metabotropic Glutamate Receptors Metabotropic Receptor Metalloprote(in)ases Methicillin-resistant Staphylococci iV-Methyl D-aspartate Receptors Methylating Agents... 

Antonov S. M. and Johnson J. W., Permeant ion regulation of IV-methyl-D-aspartate receptor channel block by Mg(2+). Proc. Natl. Acad. Sci., 96, 14571-14576, 1999. 

Anodic oxidation of a suitably unsaturated hydroxyamine was designed for the synthesis of the racemate of an 11-hydroxy metabolite of the important iV-methyl-D-aspartate receptor antagonist MK-0801 [69]. Anodic oxidation of... 

The radiosynthesis of cw-325a and trans-325b isomers of FTCP, the potent iV-methyl-D-aspartate receptor channel blocker, has been accomplished316 by displacement on... 

A less radical and much less expensive approach to the management of motor fluctuations has been described in 14 patients with advanced Parkinson s disease and levo-dopa-induced motor disorders (69). Amantadine (mean dose 350 mg/day) reduced the severity and duration of dyskinesias by 33-75%, depending on the parameter measured. The rationale was that amantadine blocked iV-methyl-D-aspartate receptors. 

Hu LA, Tang Y, Miller WE, et al. Pj-Adrenergic receptor association with PSD-95. Inhibition of receptor internalization and facilitation of pradrenergic receptor interaction with IV-methyl-D-aspartate receptors. J Biol Chem 2000 275 38,659-38,666. 

Nakagawa S. Watanabe M, Inoue Y (1996) Altered gene expression of the iV-methyl-D-aspartate receptor channel subunits in Purkinje cells of the staggerer mutant mouse. Ear J Neurosci 5 2644-2651. 

Paupard M-C, Friedman LK, Zukin RS (1997) Developmental regulation and cell-specific expression of iV-methyl-D-aspartate receptor splice variants in rat hippocampus. Neuroscience 79 399-409. 

Siegel SJ, Brose N, Janssen WG, Gasic GP, Jahn R, Heinemann SF, Morrison JH (1994) Regional, cellular, and ultrastructural distribution of iV-methyl-D-aspartate receptor subunit 1 in monkey hippocampus. Proc Natl Acad Sci USA 97 564-568. 

Strack S, Colbran RJ (1998) Autophosphorylation-dependent targeting of calcium/calmodulin-dependent protein kinase II by the NR2B subunit of the iV-methyl-D-aspartate receptor. J Biol Chem 275 20689-20692. 

Toki S, Ando K, Yoshida M, Kawamoto I, Sano H, Matsuda Y. ES-242-1, a novel compound from Verticillium sp. binds to a site on IV-methyl-D-aspartate receptor that is coupled to the channel domain. J Antibiot 45 88-93, 1992b. 

Kroemer RT, Koutsilieri E, Hecht P, Liedl KR, Riederer P, Kornhuber J. Quantitative analysis of the structural requirements for blockade of the iV-methyl-D-aspartate receptor at the phencyclidine binding site. J Med Chem 1998 41 393-400. 

Let s consider just a few of those effects in brief detail here. In the brain, lead probably corrupts more than one biochemical system. It interferes with events at nerve cell connections called glutamate synapses, which means at approximately half the synapses (connections) in the cerebral cortex. These synapses are apparently critical for learning during development. The important glutamate receptor that s involved is the so-called NMDA (iV-methyl-D-aspartate) receptor. This receptor is selectively blocked by lead, and the behavioral consequence is a deficit in learning ability. 

Postsynaptic density protein-95, which binds to the LRPl tail, might be a candidate adapter protein mediating the interaction of LRPl with the IV-methyl-D-aspartate receptor... 

Simon, R.P., Swan, J.H., Griffiths, T. and Meldrum, B.S. (1984) Blockade of iV-methyl-D-aspartate receptors may protect against ischemic damage in the brain. Science 226 850-852. 

Fig. 2.4 Diagram showing the effect of ischemic injury on glycerophospholipid-derived iipid mediators in brain. Plasma membrane (PM) iV-methyl-D-aspartate receptor (NMDA-R) giuteimate (GIu) phosphatidylcholine (PtdCho) lyso-phosphatidylcholine (lyso-PtdCho) cytosolic phospholipase A2 (CPLA2) secretory phospholipase A2 (SPLA2) cyclooxygenase (COX-2) arachidonic add (ARA) platelet-activating factor (RAF) 4-hydroxynonenal (4-HNE) reactive oxygen species (ROS) nuclear factor kappaB (NF-kB) nuclear factor kappaB response element (NF-kB-RE) inhibitory subunit of NFkB (IkB) tumor necrosis factor-a (TNF-a) interleukin-ip (IL-ip) interleukin-6 (IL-6) matrix metaUoproteinases (MMPs) positive sign (+) represents upregulation...

Marchetti L, Klein M, Schlett K, Pflzenmaier K, Eisel UL (2004) Tumor necrosis factor (TNE)-mediated neuroprotection against glutamate-induced exdtotoxicity is enhanced by iV-methyl-D-aspartate receptor activation. Essential role of a TNE receptor 2-mediated phos-phatidyUnositol 3-kinase-dependent NE-kappa B pathway. J Biol Chem 279 32869-32881 Mark RJ, Lovell MA, Markesbery WR, Uchida K, Mattson MP (1997) A role for 4-hydroxynonenal, an aldehydic produd of Upid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid p-peptide. J Neurochem 68 255-264 Mattson MP, Meffert MK (2006) Roles for NF-kappaB in nerve cell survival, plasticity, and disease. Cell Death Differ 13 852-860... 

Wheeler, D., BouteUe, M.G., and Fillenz, M. 1995. The role of iV-methyl-d-aspartate receptors in the regulation of physiologically released dopamine. Neuroscience 65 767-774. 

IV-Methyl-D-aspartate receptor density investigated by specific binding of tritiated (5R, 10S)-(+)-5-methyl-10,ll-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogenmaleate was significantly (P <0.01) decreased in the frontal cortex, the hippocampus, the striatum, and the cerebellum of male Wistar rats aged 24 months as compared with animals aged 3 months (Scheuer et al. 1999). 

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