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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 regional distribution of 9 amino acids, including glutamate and GABA and their metabolising enzymes, has been determined in 5 regions of the frog CNS. Glycine was relatively concentrated in the spinal cord whereas the highest concentration of each of the other amino acids was found in the midbrain. There was a good correlation between the activity of l-glutamate-1-carboxylase (GAD) and the level of GABA in all regions examined and both were concentrated in the midbrain. There was little regional variation in the distribution of 4-aminobutyrate-2-oxoglutarate transaminase (GABA-T).
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PMID:Glutamic acid, GABA and their metabolising enzymes in the frog central nervous system. 107 86

GAD activity and GABA, the product of GAD action on L-glutamate, are both prominent in mature human renal cortex. GAD activity is low in fetal kidney but rises several fold preterm to establish the characteristic post-term specific activity. The ontogeny of the initial step in the GABA pathway parallels the need for kidney to accommodate acid-base regulation after birth. PLP coenzyme is required for GAD holoenzyme integrity. Fetal renal GAD was frequently undersaturated with PLP in our series of observations, raising the suggestion that maternal vitamin B6 nutrition is not always adequate.
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PMID:Ontogeny of L-glutamic acid decarboxylase and gamma-aminobutyric acid concentration in human kidney. 116 51

The potential neuroprotective effects of IL-6 against the excitotoxic neuronal loss induced by N-methyl-D-aspartate (NMDA) have been studied. Infusion into the rat striatum of excitotoxic amounts (250 nmol) of NMDA resulted in a 45% decrease in striatal choline acetyl transferase activity (ChAT; a marker of cholinergic neurons) and glutamate decarboxylase (GAD, a marker of GABAergic neurons) at 2 days post-injection. Co-infusion of 10 U of IL-6 reduced the loss of ChAT activity to 21% but failed to prevent the loss of GAD activity. IL-6 per se, up to the dose of 500 U, failed to affect ChAT or GAD activities. The in vivo effects of IL-6 are not mediated by a direct antagonism of NMDA toxicity, since IL-6 (up to a concentration of 500 and 5000 U/ml, respectively) did not antagonize either the increase in cyclic GMP levels resulting from NMDA receptor activation in cerebellar slices or the glutamate-induced release of lactate dehydrogenase, an index of neurotoxicity, by cultured cortical neurons. These results suggest that the increase in IL-6 levels observed in experimental brain lesions may play a role in the protection and regeneration of cholinergic neurons.
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PMID:Local infusion of interleukin-6 attenuates the neurotoxic effects of NMDA on rat striatal cholinergic neurons. 133 14

Pig brain extracts from both soluble and membrane fractions were found to contain potent inhibitors for GABA synthesizing enzyme, GAD, referred to as endogenous GAD inhibitors (EGIs) and for the binding of GABA agonist, muscimol, referred to as muscimol binding inhibitors (MBIs). EGIs and MBIs were first purified through gel-filtration Bio-Gel P-2 columns, in which multiple activity peaks were observed. One of them appears to be co-eluted with either L-glutamate or GABA. However, others are clearly separated from L-glutamate or GABA. EGIs were found to be low MW (less than 1,800 dalton), heat and acid-base stable, negatively charged, non hydrophobic substances. MBIs were found to be low MW (less than 1,800 dalton) neutral or positively charged substances. MBIs had no effect on [3H]flunitrazepam (FNZP) binding, indicating that they are not endogenous benzodiazepine receptor ligands and they may act specifically on GABA binding site.
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PMID:Isolation and characterization of endogenous modulators for GABA system. 134 60

We report the isolation and sequencing of cDNAs encoding two human glutamate decarboxylases (GADs; L-glutamate 1-carboxy-lyase, EC 4.1.1.15), GAD65 and GAD67. Human GAD65 cDNA encodes a Mr 65,000 polypeptide, with 585 amino acid residues, whereas human GAD67 encodes a Mr 67,000 polypeptide, with 594 amino acid residues. Both cDNAs direct the synthesis of enzymatically active GADs in bacterial expression systems. Each cDNA hybridizes to a single species of brain mRNA and to a specific set of restriction fragments in human genomic DNA. In situ hybridization of fluorescently labeled GAD probes to human chromosomes localizes the human GAD65 gene to chromosome 10p11.23 and the human GAD67 gene to chromosome 2q31. We conclude that GAD65 and GAD67 each derive from a single separate gene. The cDNAs we describe should allow the bacterial production of test antigens for the diagnosis and prediction of insulin-dependent diabetes mellitus.
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PMID:Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene. 154 70

Laminer analysis of the distribution of GABA and GAD in the superior colliculus has shown that the distribution pattern of GABA within the SC is similar in rabbit, cat, and guinea pig. The highest levels of GABA were found in the superficial gray layer (SGL), averaging 37-40 mmol/kg dry weight. The GABA concentrations in the deep layers were each only half that of the levels in the SGL. The concentrations of both GABA and GAD in the upper half of SGL are the same as those in the substantia nigra and medial forebrain bundle which have the highest amounts of GABA in the CNS. Denervation studies of the fibers projecting to SGL suggest that the GABA concentrated in the SGL is intrinsic to the layer. The results obtained from immunohistochemical and electron microscopic studies on the localization of GABA neurons corresponds well with the regional distribution pattern of GABA and GAD reported here. However, pharmacological and electrophysiological studies do not necessarily accord well with the GABA distribution studies because they indicate that there are many GABA sensitive neurons in both the SGL and DGL. To investigate the role of GABA in the SGL, the effect of GABA and its agonists and antagonists on neurotransmission in SGL has been studied in SC slices in a perfusion system. Bath applied GABA (100 microM to 1 mM) enhanced the amplitude of postsynaptic field potentials (PSP) in SGL in a dose-dependent fashion and at concentrations above 1 mM it depressed the PSP in a dose-dependent fashion. A similar response pattern was obtained with muscimol (0.1-10 microM excitation; greater than 10 microM inhibition). However (-)-baclofen only inhibited the PSP. Bicuculline (1 microM) shifted the dose-response inhibitory curve of GABA to the right, while the excitatory effect was enhanced. These results indicate that GABA has an excitatory and inhibitory action on neurotransmission in the SGL. The nigro-tectal GABAergic fibers terminate in the intermediate and deep layers of SC. Inhibition of GABAergic activity in the SC causes irrepressible saccades made toward the center of the movement field while GABA activation delays and slows saccadic eye movements. Thus, GABA in the SC plays an important role in the control of eye movements. The same GABAergic projection is also related to the propagation of generalized seizures. There exist collicular neurons which suppress the propagation of seizures.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The distribution and function of gamma-aminobutyric acid (GABA) in the superior colliculus. 163 1

gamma-Aminobutyric acid (GABA) synthesis was studied in rat brain synaptosomes by measuring the increase of GABA level in the presence of the GABA-transaminase inhibitor gabaculine. The basal rate of synaptosomal GABA synthesis in glucose-containing medium (25.9 nmol/h/mg of protein) was only 3% of the maximal activity of glutamate decarboxylase (GAD; 804 +/- 83 nmol/h/mg of protein), a result indicating that synaptosomal GAD operates at only a small fraction of its catalytic capacity. Synaptosomal GABA synthesis was stimulated more than threefold by adding 500 microM glutamine. Glutamate also stimulated GABA synthesis, but the effect was smaller (1.5-fold). These results indicate that synaptosomal GAD is not saturated by endogenous levels of its substrate, glutamate, and account for part of the unused catalytic capacity. The greater stimulation of GABA synthesis by glutamine indicates that the GAD-containing compartment is more accessible to extrasynaptosomal glutamine than glutamate. The strong stimulation by glutamine also shows that the rates of uptake of glutamine and its conversion to glutamate can be sufficiently rapid to support GABA synthesis in nerve terminals. Synaptosomes carried out a slow net synthesis of aspartate in glucose-containing medium (7.7 nmol/h/mg of protein). Aspartate synthesis was strongly stimulated by glutamate and glutamine, but in this case the stimulation by glutamate was greater. Thus, the larger part of synaptosomal aspartate synthesis occurs in a different compartment than does GABA synthesis.
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PMID:Stimulation of synaptosomal gamma-aminobutyric acid synthesis by glutamate and glutamine. 196 57

L-Glutamic acid decarboxylase (GAD; EC 4.1.1.15) was purified to apparent homogeneity from the brain of the locust Schistocerca gregaria using a combination of chromatofocusing (Mono P) and gel filtration (Superose 12) media. The homogeneity of the enzyme preparation was established by native polyacrylamide gel electrophoresis (PAGE) with silver staining. The molecular weight of the purified enzyme was estimated from native gradient gel electrophoresis and gel filtration chromatography to be 97,000 +/- 4,000 and 93,000 +/- 5,000, respectively. When analysed by sodium dodecyl sulphate-PAGE, the enzyme was found to be composed of two distinct subunits of Mr 51,000 +/- 1,000 and 44,000 +/- 1,500. Tryptic peptide maps of iodinated preparations of these two subunits showed considerable homology, suggesting that the native enzyme is a dimer of closely related subunits. The purified enzyme had a pH optimum of 7.0-7.4 in 100 mM potassium phosphate buffer and an apparent Km for glutamate of 5.0 mM. The enzyme was strongly inhibited by the carbonyl-trapping reagent aminooxyacetic acid with an I50 value of 0.2 microM.
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PMID:A rapid purification of L-glutamic acid decarboxylase from the brain of the locust Schistocerca gregaria. 276 57

The technique of estimating gamma-aminobutyric acid (GABA) turnover by inhibiting its major degrading enzyme GABA-T (4-aminobutyrate:2-oxoglutarate aminotransferase; EC 2.6.1.19) and measuring GABA accumulation has been used repeatedly, but, at least in rats, its usefulness has been limited by several difficulties, including marked differences in the degree of GABA-T inhibition in different brain regions after systemic injection of GABA-T inhibitors. In an attempt to improve this type of approach for measuring GABA turnover, the time course of GABA-T inhibition and accumulation of GABA in 12 regions of rat brain has been studied after systemic administration of aminooxyacetic acid (AOAA), injected at various doses and with different routes of administration. A total and rapidly occurring inhibition of GABA-T in all regions was obtained with intraperitoneal injection of 100 mg/kg AOAA, whereas after lower doses, marked regional differences in the degree of GABA-T inhibition were found, thus leading to underestimation of GABA synthesis rates, e.g., in substantia nigra. The activity of the GABA-synthesizing enzyme GAD (L-glutamate-1-decarboxylase; EC 4.1.1.15) was not reduced significantly at any time after intraperitoneal injection of AOAA, except for a small decrease in olfactory bulbs. Even the highest dose of AOAA tested (100 mg/kg) was not associated with toxicity in rats, but induced motor impairment, which was obviously related to the marked GABA accumulation found with this dose. The increase in GABA concentrations induced with intraperitoneal injection of 100 mg/kg AOAA was rapid in onset, allowing one to estimate GABA turnover rates from the initial rate of GABA accumulation, i.e., during the first 30 min after AOAA injection. GABA turnover rates thus determined were correlated in a highly significant fashion with the GAD activities determined in brain regions, with highest turnover rates measured in substantia nigra, hypothalamus, olfactory bulb, and tectum. Pretreatment of rats with diazepam, 5 mg/kg i.p., 5-30 min prior to AOAA, reduced the AOAA-induced GABA accumulation in all 12 regions examined, most probably as a result of potentiation of postsynaptic GABA function. The data indicate that AOAA is a valuable tool for regional GABA turnover studies in rats, provided the GABA-T inhibitor is administered in sufficiently high doses to obtain complete inhibition of GABA degradation.
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PMID:Use of inhibitors of gamma-aminobutyric acid (GABA) transaminase for the estimation of GABA turnover in various brain regions of rats: a reevaluation of aminooxyacetic acid. 280 89

The topographical distribution of glutamate uptake, GABA uptake, and GAD activity was studied in caudal, intermediate and rostral areas of the nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus (DMN) and the of the solitary tract (NTS), dorsal motor nucleus of the vagus (DMN) and the hypoglossal nucleus (n.XII). Within the NTS and n.XII, all three neurochemical parameters exhibited increasing activity from caudal to rostral regions. The distribution pattern for glutamate uptake within the DMN was qualitatively similar to the other nuclei studied, whereas GABA uptake and GAD activity were found to be homogeneously distributed within the DMN. The NTS also exhibited a medial-lateral heterogeneity for glutamate and GABA uptake, with the medial aspect of this nucleus containing significantly higher uptake than the lateral aspect.
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PMID:Neurochemical studies of the nucleus of the solitary tract, dorsal motor nucleus of the vagus and the hypoglossal nucleus in rat: topographical distribution of glutamate uptake, GABA uptake and glutamic acid decarboxylase activity. 285


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