Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:6893-26-1 (glutamate)
 73,096 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endogenous factor that inhibited 3H-L-glutamate specific binding (FIB) was isolated from the aqueous extract of the crude mitochondrial fraction of the rat cerebral cortex homogenate and partially purified. The purification procedure involved several steps of ion-exchange, gel-permeating and thin-layer chromatography. Partially purified FIB competitively inhibited 3H-L-glutamate specific binding and had the molecular weight of 450-600 Da. Glutamic acid residues were found in FIB amino acids. The functional role of the isolated factor as an endogenous modulator involved in the regulation of effective synaptic transmission of glutamatergic brain synapses is discussed.
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PMID:[Isolation and partial purification of the endogenous inhibitor of receptor binding of 3H-L-glutamate]. 287 47

The effects of L-glutamate and other dicarboxylic amino acids on the accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in slices of cerebral cortex from strain 2 guinea pigs were examined using tissue from animals at 39 days gestation to 7 days after birth. Responses to glutamate were inhibited completely by adenosine deaminase or theophylline unless histamine was present. When tested in the presence of adenosine, glutamate increased cyclic AMP accumulation up to 10-fold at 39 days gestation; the response was maximal at 52 days gestation, and both the efficacy and potency of glutamate declined thereafter. While the effects of glutamate were smaller in the presence of histamine plus theophylline, the developmental pattern was similar to that in the presence of adenosine. The relative potencies of D-aspartate, kainate, and alpha-methyl-DL-glutamate were much greater in fetal than in adult tissue. Glutamic acid diethyl ester, N-acetyl glutamate or 2,3-diaminopropionate had no effect in fetal tissue either in the presence or absence of glutamate. Responses to glutamate in adult tissue were much more dependent upon the presence of calcium ions than were those in fetal tissue. It was concluded that responses to glutamate involve mechanisms that differ in fetal and adult tissue.
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PMID:Ontogeny of adenosine 3',5'-monophosphate metabolism in guinea pig cerebral cortex. II. Development of responses to L-glutamate in the presence of adenosine or histamine. 288 13

Extracellular records were made from subthalamic nucleus neurons during microiontophoretic application of drugs and stimulation of the corticosubthalamic nucleus pathway. In 87% of the subthalamic nucleus cells, cortical stimulation induced a powerful excitation, consisting of a burst of 1-7 spikes. This projection must arise from a large area of the cortex since stimulation of nearly all the ipsilateral cortex and the rostral two-thirds of the contralateral cortex was found to influence the activity of subthalamic nucleus neurons. Experiments were undertaken in order to determine the identity of the neurotransmitter involved in the corticosubthalamic nucleus pathway. Glutamic acid diethyl ester reversibly suppressed subthalamic nucleus excitations induced by ipsi- or contralateral cortical stimulation or microiontophoretically applied glutamate. On the same cells, this compound had no effect on acetylcholine-evoked excitation and gamma-aminobutyric acid-evoked inhibition and subthalamic excitation induced by stimulation of the tegmenti pedunculopontine nucleus. Atropine at doses which antagonized the acetylcholine response, flupenthixol at dose which antagonized the dopamine response, and bicuculline at doses which antagonized the gamma-aminobutyric acid response failed to block excitations evoked by cortical stimulation and by glutamate. These experiments excluded a role for acetylcholine, dopamine and gamma-aminobutyric acid in the cortically evoked excitation of subthalamic nucleus cells. Since an amino acid seemed to play a role as neurotransmitter of the corticosubthalamic nucleus pathway, further experiments were designed to confirm these data and to determine the contribution of each amino acid receptor type in the cortical-induced excitation of subthalamic cells. All the subthalamic cells recorded were also excited by microiontophoretically applied N-methyl-D-aspartic, quisqualic and kainic acids. The cortical-evoked activation of subthalamic nucleus neurons was reversibly suppressed by kynurenic acid and cis-2,3-piperidine dicarboxylic acid, two broad-spectrum antagonists of excitatory amino acids, microiontophoretically applied at doses which also blocked excitations induced by N-methyl-D-aspartic, quisqualic and kainic acids. Application of 2-amino-5-phosphonovaleric acid inhibited excitation induced by N-methyl-D-aspartic acid but not those elicited by quisqualic or kainic acid, while glutamate excitation was only slightly affected. This compound had no effect on the cortically evoked excitation of subthalamic nucleus neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacological study of the cortical-induced excitation of subthalamic nucleus neurons in the rat: evidence for amino acids as putative neurotransmitters. 288 55

In the vertebrate retina excitatory transmission seems to be mediated mainly by excitatory amino acids; glutamate and/or aspartate are the most viable candidates to subserve this function. Postsynaptic receptors for N-methyl-D-aspartate (NMDA), kainate (KA), quisqualate (QA) and 2-amino-4-phosphonobutyric acid have been electrophysiologically identified. In this work we have tried to identify and characterize QA receptors through the binding of the most specific analogue available for this receptor: [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA). AMPA binding to retinal membranes was sodium- and temperature-independent, with optimum pH at 6-7. Ligand-receptor interaction was reversible and saturable. Pharmacologically, glutamate analogues were more active displacers than NMDA analogues: AMPA greater than (RS)-3-hydroxy-4,5,6,7-tetrahydro-isoxazolo-(5,4-C)-pyridine-7-car boxylic acid = L-Glu = QA; with IC50 in the low microM range. Glutamic acid diethylester was uneffective while KA and cis-2,3-piperidine dicarboxylate were potent inhibitors of binding. Binding was stereospecific, L-isomers being more effective displacers than D-forms. Subcellular distribution showed binding concentrated in the inner plexiform layer (IPL), but also present in the outer plexiform layer (OPL). Kinetics of [3H]AMPA binding showed a high affinity kB = 1-2 microM in membranes from complete retina, IPL and OPL, with binding sites concentrated in P2 (Bmax = 16.2 pmol/mg protein). Our results provide biochemical evidence for the presence and distribution of physiologically relevant QA receptors in the chick retina which is in agreement with previous physiological findings.
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PMID:Characterization of quisqualate-type L-glutamate receptors in the retina. 288 40

Amino acid contents were measured in autopsied brains of eight patients with the sporadic form of amyotrophic lateral sclerosis (ALS) and in brains of control subjects dying without neurologic or psychiatric disease. Glutamic acid content was reduced in most brain regions and in the cervical cord in the ALS patients, while glutamine contents were normal. Taurine contents were increased, and gamma-aminobutyric acid contents were decreased in some brain regions in the ALS patients. The brain glutamate deficiency in ALS is unexplained, but insufficient production or release of this excitatory neurotransmitter might have important secondary effects on motor neurons.
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PMID:Brain glutamate deficiency in amyotrophic lateral sclerosis. 289 Oct 83

Glutamic acid is an excitatory neurotransmitter that may have a significant role in the central chemical drive of ventilation. Therefore cardiorespiratory function was measured in pentobarbital sodium-anesthetized dogs before and after central inhibition of glutamate metabolism by means of methionine sulfoximine (MSO), a specific inhibitor of glutamine synthase (GS) catalyzing amidation of glutamate to glutamine. GS was inhibited centrally by perfusing the ventriculocisternal space with artificial cerebrospinal fluid (CSF) containing 92.5 mmol MSO per liter at a fixed pH, perfusion rate, and pressure. After GS inhibition, CSF transfer rate of [13N]glutamine synthesized from 13NH4+ amidation of glutamate was reduced five-fold, and minute ventilation increased from 2.90 +/- 0.41 (SE) l/min (0.164 +/- 0.020 l.min-1.kg body wt-1) to 4.46 +/- 0.52 l/min (0.254 +/- 0.029 l.min-1.kg body wt-1). This increase in ventilation with endogenous glutamate and the increase in ventilation previously observed during ventriculocisternal perfusion of exogenous glutamate are compared quantitatively via a model of central neurotransmitter glutamate chemoreception. The results support the hypothesis that the endogenous brain glutamate is important in the central chemical drive of ventilation.
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PMID:Central respiratory effects of glutamine synthesis inhibition in dogs. 290 34

Ampullae of Lorenzini isolated from the skate (Raja clavata) have been investigated in vitro electrophysiologically to determine the nature of the transmitter at the synapse between the electroreceptor cells and afferent fibres. Glutamic acid diethyl ester (GDEE), glutamic acid dimethyl ester (GDME), kynurenic acid (KENYA), cis-2,3-piperidine dicarboxylic acid (PDA) reversibly decreased the resting and stimulus-induced activity. These antagonists also blocked postsynaptic responses induced by glutamate and aspartate. D-alpha-aminoadipic acid (DAA) had no effect on the afferent activity. These findings suggest that glutamate, aspartate or a related compound may be a transmitter at this synapse. An important physiological role of quisqualate receptors in ampullae of Lorenzini is also inferred from these experiments.
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PMID:[Effect of antagonists of excitatory amino acids on synaptic transmission in the electroreceptors (Lorenzini's ampullae) in skates]. 290 59

Glutamic acid diethyl ester (GDEE) is a glutamate antagonist which acts preferentially at the quisqualate-sensitive receptor and has been shown to be an effective anticonvulsant in alcohol withdrawal and homocysteine-induced seizures but ineffective in other seizure models. To better characterize the role of the quisqualate-sensitive receptor in the generation of seizures, quisqualate was administered to mice by intracerebroventricular (ICV) route and immediate onset generalized seizures were observed. The anticonvulsant properties of GDEE and commonly used antiepileptic drugs (AEDs) were investigated with this seizure model. GDEE given by intraperitoneal blocked quisqualate-induced seizures dose-dependently. Diphenyl-hydantoin (50 mg/kg IP), carbamazepine (50 mg/kg IP), diazepam (1; 4 mg/kg IP), phenobarbital (40; 80 mg/kg IP), and valproic acid (250; 340 mg/kg IP) were also administered prior to quisqualate-seizure induction. Only valproic acid blocked seizures at nonsedating doses. The GABA transaminase inhibitor aminooxyacetic acid (20 mg/kg IP) was ineffective, suggesting that here valproic acid is active at excitatory receptors rather than by potentiating GABA post-synaptic inhibition. These data are consistent with the hypothesis that the quisqualate-sensitive receptor is involved in some forms of clinically observed seizures, particularly those which are controlled by valproic acid.
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PMID:Inhibition of quisqualate-induced seizures by glutamic acid diethyl ester and anti-epileptic drugs. 310 Jul 18

Glutamic acid 1-semialdehyde hydrochloride was synthesized and purified. Its prior structural characterization was extended and confirmed by 1H NMR spectroscopy and chemical analyses. In aqueous solution at pH 1 to 2 glutamic acid 1-semialdehyde exists in a stable hydrated form, but at pH 8.0 it has a half-life of 3 to 4 min. Spontaneous degradation of the material at pH 8.0 generated some undefined condensation products, but coincidentally a significant amount isomerized to 5-aminolevulinate. At pH 6.8 to 7.0, glutamate 1-semialdehyde is sufficiently stable to permit routine and reproducible assay for glutamate 1-semialdehyde aminotransferase activity. Only about 20% of the enzyme extracted from chloroplasts was sensitive to inactivation by gabaculine with no pretreatment. However, when the enzyme was exposed to 5-aminolevulinate, levulinate or 4,5-dioxovalerate in the absence of glutamate 1-semialdehyde, it was completely inactivated by gabaculine; 4,6-dioxoheptanoate had no effect on the enzyme. These results lead to the hypothesis that the aminotransferase exists in the chloroplast in a complex with pyridoxamine phosphate, which must be converted to the pyridoxal form before it can form a stable adduct with gabaculine. We propose that the enzyme catalyzes the conversion of glutamate 1-semialdehyde to 5-aminolevulinate via 4,5-diaminovalerate.
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PMID:Biosynthesis of delta-aminolevulinate in greening barley leaves. IX. Structure of the substrate, mode of gabaculine inhibition, and the catalytic mechanism of glutamate 1-semialdehyde aminotransferase. 325 6

Homocysteine thiolactone causes convulsions when administered to animals, and has recently been reported to have excitatory effects on neurons in the central nervous system. Glutamic acid diethyl ester (GDEE) has previously been found to be an effective antagonist of the central excitation induced by homocysteine and is thought to be a selective antagonist of the quisqualate-sensitive excitatory amino-acid-receptor site. If an interaction of homocysteine with the quisqualate-sensitive receptor site is responsible for its convulsive properties, GDEE might also block the induction of seizures by homocysteine. GDEE in a dosage of 4 mmol/kg almost completely blocked homocysteine-induced seizures in mice; smaller dosages had no effect or only slight inhibitory effects. Glutamic acid dimethyl ester (GDME) and glutamic acid gamma-methyl ester (GMME) also partially blocked homocysteine-induced seizures, but monosodium glutamate and glutamic acid gamma-monoethyl ester (GMEE) had only a slight effect. None of the glutamate esters inhibited seizures induced by pentylenetetrazole. It is therefore suggested that certain types of seizures involve the quisqualic acid excitatory amino-acid-receptor site. Homocysteine-induced seizures may serve as a model of seizures of this type, and GDEE, GDME, and GMME may be effective antagonists of such seizures.
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PMID:Selective inhibition of homocysteine-induced seizures by glutamic acid diethyl ester and other glutamate esters. 397 49


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