Disease relevance of POLYGLUTAMIC ACID

• Excitation mediated by dicarboxylic amino acids such as L-glutamate or L-aspartate, has been claimed to be involved in pathogenesis of neurodegenerative disorders [1].
• In support of this hypothesis, NMDA receptor antagonists reduce the volume of infarction produced by occlusion of the middle cerebral artery in vivo and attenuate Ca2+ influx and neuronal death elicited by L-glutamate or NMDA in vitro [2].
• Microinjection of L-glutamate into the intermediate nucleus tractus solitarii in anesthetized rats elicits hypotension, bradycardia, and apnea, simulating baroreceptor reflexes [3].
• L-Glutamate is a potent neurotoxin, and the inadequate clearance of excitatory amino acids may contribute to the neurodegeneration seen in a variety of conditions, including epilepsy, ischemia, and amyotrophic lateral sclerosis [4].
• In this study, we determined the crystal structure of the 'non-productive' complex of Thermus thermophilus GluRS, ATP and L-glutamate, together with those of the GluRS.ATP, GluRS.tRNA.ATP and GluRS.tRNA.GoA (a glutamyl-AMP analog) complexes [5].

Psychiatry related information on POLYGLUTAMIC ACID

• L-phosphoserine, a metabolite elevated in Alzheimer's disease, interacts with specific L-glutamate receptor subtypes [6].
• The electrode showed low detection limits (LOD = 0.98 +/- 0.09 microM, signal-to-noise ratio of 3), fast response times (T90 approximately 1 s), and excellent linearity (R2 = 0.999 +/- 0.000) over the concentration range of 0-200 microM for calibrations of L-glutamate in vitro [7].
• Microinjection of 3.0 microg L-glutamate kept animals awake for 2-3 h by eliminating slow-wave and REM sleep [8].
• Microinjection of the excitatory amino acid, L-glutamate into the brainstem pedunculo pontine tegmentum (PPT) has been shown to induce wakefulness, however, it has been unclear that receptors mediate this effect [9].
• A growing body of evidence suggests that perturbations in systems using the excitatory amino acid L-glutamate (L-Glu) may underlie the pathogenic mechanisms of (e.g.) hypoxia-ischemia, epilepsy, and chronic neurodegenerative disorders such as Huntington's disease and AD [10].

High impact information on POLYGLUTAMIC ACID

• Excitatory amino-acid carrier 1 (EAAC1) is a high-affinity Na+-dependent L-glutamate/D,L-aspartate cell-membrane transport protein [11].
• The cloned receptors negatively couple to adenylyl cyclase and show sequence similarity to the metabotropic receptors for the excitatory neurotransmitter L-glutamate [12].
• Here we report that, unlike AMPA which stimulates, kainate elicits a dose-dependent decrease in L-glutamate release from rat hippocampal synaptosomes and also depresses glutamatergic synaptic transmission [13].
• The transport activity encoded by EAAT4 has high apparent affinity for L-aspartate and L-glutamate, and has a pharmacological profile consistent with previously described cerebellar transport activities [14].
• Expression of this cDNA in transfected HeLa cells indicates that L-glutamate accumulation requires external sodium and internal potassium and transport shows the expected stereospecificity [15].

Chemical compound and disease context of POLYGLUTAMIC ACID

• Meanwhile, supersensitization of increase in L-glutamate release to nanomolar levodopa was seen in Parkinson's model rats, which may relate to dyskinesia or "on-off" during chronic therapy [16].
• gamma-Aminobutyric acid concentration, L-glutamate 1-decarboxylase activity, and properties of the gamma-aminobutyric and postsynaptic receptor in cobalt epilepsy in the rat [17].
• Escherichia coli cells cultured with succinate as the carbon source display apparent K-m values for the uptake of L-glutamate of 10 muM in the absence of added sodium ion and 0.7 muM in the presence of an optimal level of sodium ion (15 to 50 mM) [18].
• The structure and biosynthesis of new tetrahydropyrimidine derivatives in actinomycin D producer Streptomyces parvulus. Use of 13C- and 15N-labeled L-glutamate and 13C and 15N NMR spectroscopy [19].
• A novel reaction catalyzed by unadenylylated glutamine synthetase from Escherichia coli. AMP-dependent synthesis of pyrophosphate and L-Glutamate from orthophosphate and L-glutamine [20].

Biological context of POLYGLUTAMIC ACID

• Fodrin has been hypothesized to regulate the number of receptor binding sites on neuronal membranes for the putative neurotransmitter L-glutamate [21].
• In order to study the kinetics of release of endogenous L-glutamate from guinea pig cerebral cortical synaptosomes we have devised a continuous enzymatic assay [22].
• Recent study of the ventral muscle fibres in the larvae of the beetle, Tenebrio molitor, has revealed that the transmitter action can be mimicked by the iontophoretic application of L-glutamate to the junctional sites at which the extracellular excitatory postsynaptic potentials (e.p.s.ps) could be recorded (D.Y. and H.W., unpublished observation) [23].
• We now report that chronic intracortical administration of L-glutamate during a period of monocular vision imposed on young kittens largely prevents the ocular dominance shift which normally occurs under these circumstances [24].
• In hippocampal neurons, L-glutamate, an inducer of Ca2+ influx and calcineurin activation, triggered mitochondrial targeting of BAD and apoptosis, which were both suppressible by coexpression of a dominant-inhibitory mutant of calcineurin or pharmacological inhibitors of this phosphatase [25].

Anatomical context of POLYGLUTAMIC ACID

• Fast excitatory transmission in the vertebrate central nervous system is mediated mainly by L-glutamate [26].
• Here, we report that [3H]-D-AP5 binds specifically to rat brain membranes, that the hippocampus and cerebral cortex are enriched in these sites relative to other brain areas and that L-glutamate has higher affinity for these receptors than have all other transmitter candidates tested [27].
• We report that dopamine and cyclic AMP, although having little direct effect on resting membrane conductance, greatly enhance ionic conductances gated by kainate, an agonist of the transmitter released by the photoreceptors, and by L-glutamate, the agent proposed to be the photoreceptor transmitter [28].
• Evidence for L-glutamate as the neurotransmitter of baroreceptor afferent nerve fibers [3].
• Gamma-aminobutyrate acid, L-glutamate, and N-methyl-D-aspartate were separated by capillary electrophoresis and detected by the use of whole-cell and outside-out patch-clamp techniques on freshly dissociated rat olfactory interneurons [29].

Associations of POLYGLUTAMIC ACID with other chemical compounds

• In the mammalian central nervous system amino acids such as L-glutamate and L-aspartate are thought to act as fast synaptic transmitters [30].
• In the central nervous system (CNS), the principal mediators of fast synaptic excitatory neurotransmission are L-glutamate-gated ion channels that are responsive to the glutamate agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) [31].
• The microiontophoretic application of thyrotropin-releasing hormone causes a selective reduction in neuronal excitation evoked by L-glutamate but not by acetylcholine in rat cerebral cortex [32].
• In conscious rats, these GLU(K5) antagonists prevented and interrupted limbic seizures induced by intra-hippocampal pilocarpine perfusion, and attenuated accompanying rises in extracellular L-glutamate and GABA [33].
• After growth of C. albicans in 20 mM D-glucose, as opposed to 20 mM L-glutamate, flow cytometric analysis with monoclonal antibodies recognizing the alpha-subunit of CD11b/CD18 demonstrated a 25.0% increase in mean channel fluorescence (range 18.4-31.8%), as well as an increased percentage of yeasts fluorescing (P less than 0.02) [34].

Gene context of POLYGLUTAMIC ACID

• In 293 cells expressing NR1-NR2A channels dithiothreitol (DTT) rapidly potentiated L-glutamate-activated whole-cell currents and decreased the time course of desensitization and deactivation [35].
• The affinities of the EAAT subtypes for L-glutamate were similar, with Km determinations varying from 48 to 97 microM in the mammalian cell assay and from 18 to 28 microM in oocytes [36].
• Glutamate dehydrogenase is found in all organisms and catalyses the oxidative deamination of l-glutamate to 2-oxoglutarate [37].
• Coexpression of postsynaptic density-95 protein with NMDA receptors results in enhanced receptor expression together with a decreased sensitivity to L-glutamate [38].
• Exposure of the cells to L-glutamate (100-1000 microM) resulted in an increase in phosphorylated p44/42 MAPK (ERK1/2) in a concentration- and time-dependent manner [39].

Analytical, diagnostic and therapeutic context of POLYGLUTAMIC ACID

• Effect of denervation and local damage on extrajunctional L-glutamate receptors in locust muscle [40].
• To address this question, we loaded the excitatory transmitter L-glutamate via whole-cell recording pipettes into the giant nerve terminal, the calyx of Held, in rat brainstem slices [41].
• The distribution of glutamine synthetase [L-glutamate: ammonia ligase (ADP-forming), EC 6.3.1.1)] among rat liver parenchymal cells in situ and in primary culture was investigated by indirect immunofluorescence using a specific antiserum [42].
• In our experiments, iontophoresis of the sodium salt of synthetic NAAG did not induce single-unit spiking at sites in slices of rat piriform cortex that responded vigorously to L-glutamate [43].
• The effect of amino acid L-glutamate on the extended preservation ex vivo of the heart for transplantation [44].

References