Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.1.1.15 (glutamate decarboxylase)
2,169 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cultured human neuroblastoma cell lines were assayed for biochemical characteristics of neuonal function. Cell lines studied included LA-N-1, LA-N-2, IMR-32, SK-N-SH, and SK-N-MC. Veratridine-dependent uptake of 22Na+ implied the presence of the action potential Na+ ionophore in LA-N-1, LA-N-2, IMR-32, and SK-N-SH. The time course of 22Na+ uptake and inhibition of uptake by tetrodotoxin supported this. SK-N-MC had no veratridine-dependent 22Na+ uptake. Tyrosine hydroxylase (EC 1.14.10.), glutamic acid decarboxylase (EC 4.1.1.15), and acetylcholine contents in neuroblastoma cells were compared to those in brain. LA-N-1 and IMR-32 contained 15 and 5 times as much tyrosine hydroxylase, respectively, whereas LA-N-2, SK-N-SH, and SK-N-MC contained only 0.5 to 5% of that in brain. Acetylcholine was present in -LA-N-2 in 15- to 20-fold greater quantities than in brain; other lines had only 10 to 50% of that in brain. None of the cell lines contained glutamic acid decarboxylase. Thus, continuously propogated human neuroblastoma cell lines may have the action potential Na+ ionophore and may be adrenergic (LA-N-1 and IMR-32), cholinergic (LA-N-2), or inactive (SK-N-SH and SK-N-MC). This is the first demonstration of the action potential Na+ ionophore and of acetylcholine production in human neuroblastoma cell lines.
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PMID:Adrenergic, cholinergic, and inactive human neuroblastoma cell lines with the action-potential Na+ ionophore. 1 22

Nigral basal adenylate cyclase and dopamine-sensitive adenylate cyclase, glutamate decarboxylase, choline acetyltransferase, and tyrosine hydroxylase activities were measured in rats with hemitransections at various levels or with electrolytic lesions of the medial forebrain bundle or the crus cerebri. The loss of nigral dopamine-sensitive adenylate cyclase activity after the various brain lesions was correlated with loss of nigral glutamic acid decarboxylase but not that of tyrosine hydroxylase; nigral choline acetyltransferase was unaffected in all cases. The data indicate that the nigral dopamine-sensitive adenylate cylase activity may be localized on neurons afferent to the nigra, probably originating from the globus pallidus and possibly from the tail of the caudate. The results suggest that dopamine, released from nigral dendrites, may influence dopaminergic activity indirectly by modulating impulses transmitted to the nigrostriatal neurons through the crus cerebri.
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PMID:Localization of nigral dopamine-sensitive adenylate cyclase on neurons originating from the corpus striatum. 1 59

Specific inhibition of glutamic acid decarboxylase (GAD, EC 4.1.1.15; the main enzyme involved in the synthesis of gamma-aminobutyric acid) by mercaptopropionic acid interferes with the effect of dexamethasone on both the resting and stress-induced secretion of ACTH. It is postulated that dexamethasone may, at least in part, inhibit the secretion of ACTH via the induction of GAD, thereby raising the level of gamma-aminobutyric acid in the central nervous system.
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PMID:Possible role of gamma-aminobutyric acid synthesis in the mechanism of dexamethasone feedback action. 20 22

gamma-Aminobutyric acid (GABA) is an inhibitory neurotransmitter in the peripheral nervous system of certain invertebrates and is thought to be a major transmitter in the vertebrate central nervous system. In this report we present evidence that GABA may also be a neurotransmitter in the vertebrate peripheral autonomic nervous system. We have used light and electron microscopic autoradiography to analyse high-affinity uptake of 3H-GABA into the myenteric plexus of the guinea pig taenia coli, both in situ and in a tissue culture preparation. In the isolated myenteric plexus, we have measured the specific activity of glutamic acid decarboxylase (GAD; EC 4.1.1.15), the enzyme responsible for conversion of glutamic acid to GABA in GABAergic neurones, and assessed the ability of this tissue to accumulate 3H-GABA newly synthesised from 3H-glutamic acid. Furthermore, we have measured the levels of endogenous GABA in strips of taenia coli containing the myenteric plexus.
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PMID:GABA may be a neurotransmitter in the vertebrate peripheral nervous system. 55 Dec 69

The in vivo effects of convulsant drugs (hydrazine and penicillamine) on the metabolism of gamma-aminobutyric acid (GABA) in subcellular fractions of mouse brain were studied. Both substances inhibited the activity of glutamic acid decarboxylase [EC 4.1.1.15] (GAD) in the synaptosomal fraction (nerve ending particles) and reduced the concentration of GABA in the same fraction at the onset of convulsions, though changes in the total GABA concentration in the brain did not correlate with the onset of convulsions. Therefore, it is suggested that the concomitant decrease of GAD activity and GABA concentration in the nerve endings, independently of the total GABA concentration, is probably an important factor in the onset of some kinds of convulsions.
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PMID:gamma-Aminobutyric acid metabolism in subcellular particles of mouse brain and its relationship to convulsions. 89 80

The catalytic activity of the enzyme L-glutamic acid decarboxylase (GAD) is determined by an amperometric method based on a recently developed glutamate-selective biosensor. The biosensor is composed of an amperometric H2O2 electrode and a biocatalytic membrane containing the enzyme glutamic acid oxidase (GAO). The biosensor allows the direct and continuous measurement of GA levels by monitoring the H2O2 produced at the electrode interface as a coproduct of the GAO-catalyzed GA oxidation to alpha-ketoglutaric acid. Since GA is transformed to gamma-aminobutyric acid and CO2 under the catalytic activity of GAD, the rate of GA consumption in solution, monitored by the GAO biosensor, represents a reliable measure of GAD catalytic activity. Additional experiments performed in the presence of different concentrations of the GAD inhibitor valproic acid have shown the suitability of the proposed approach for the study of GAD inhibitors also. Discussion of the main experimental characteristics of this new analytical method is given in terms of sensitivity, reproducibility, and reliability of the experimental results and ease, time, and cost of operation.
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PMID:Determination of glutamic acid decarboxylase activity and inhibition by an H2O2-sensing glutamic acid oxidase biosensor. 135 47

Secretory vesicles of both the exocrine and the endocrine pancreas have been isolated and characterized in molecular terms from pancreatic tissue and primary cell cultures. Studies on pancreatic secretory processes could be further facilitated by the use of permanent cell lines that respond to secretory stimuli with a regulated secretory response. We now present biochemical, morphological and secretory studies on the rat pancreatic acinar cell line AR42J. This cell line is characterized by the presence of digestive enzyme-containing dense core vesicles, which are released in response to cholecystokinin. In addition, we present evidence that these cells also contain small neuroendocrine-specific vesicles, as evidenced by the expression of the neuroendocrine-specific vesicle proteins synaptophysin and S.V.2. Corresponding to these mixed exocrine-neuroendocrine features, we also found considerable amounts of the neurotransmitters glycine, glutamine and gamma-aminobutyric acid (GABA), as well as the rate-limiting enzyme in GABA synthesis, glutamic acid decarboxylase (GAD) (EC 4.1.1.15) expressed in these cells. We demonstrated a specific uptake mechanism for radioactively-labelled GABA by these cells. In addition, GABA was released from intracellular storage pools by nicotinic receptor stimulation or membrane depolarization. In summary, AR42J cells represent the first amphicrine pancreatic cell line with the combined expression of exocrine and neuroendocrine secretory organelles, both of which follow a regulated secretory pathway in response to various secretory stimuli.
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PMID:The amphicrine pancreatic cell line AR42J: a model system for combined studies on exocrine and endocrine secretion. 135 76

Insulin-dependent diabetes mellitus (IDDM) is associated with serum antibodies that precipitate a 64-kDa pancreatic islet cell protein reported to be glutamic acid decarboxylase (GAD; glutamate decarboxylase, EC 4.1.1.15). Previously, antibodies to GAD were found in the rare neurological disorder stiff man syndrome. To demonstrate directly antibodies to GAD, enzymatically active GAD was first purified from fresh human cerebellum. Brain GAD activity was precipitated by noninhibitory antibodies in the sera of 16/26 (62%) subjects defined as having preclinical IDDM (islet cell antibody-positive first-degree relatives of a person with IDDM), 3/13 (23%) with recent-onset IDDM, and 3/3 with the stiff man syndrome. In addition, sera of 5/26 (19%) preclinical and 2/13 (15%) recent-onset IDDM subjects contained antibodies that precipitated GAD but inhibited its activity. Thus, overall, 21/26 (81%) preclinical and 5/13 (38%) recent-onset IDDM subjects had antibodies that precipitated GAD activity. Antibodies to GAD were not detected in sera from subjects with other autoimmune diseases (n = 29) or healthy controls (n = 14). GAD affinity-purified to homogeneity (specific activity, 58 units/mg) was specifically immunoprecipitated as a single 60-kDa species by the IDDM sera. In an ELISA incorporating whole mouse brain GAD captured by the GAD-6 monoclonal antibody the frequencies of GAD antibodies for all subject groups were indistinguishable from those found by precipitation of human brain enzymatic activity. We conclude that (i) GAD is an (auto)antigen in a majority of subjects operationally defined as having preclinical IDDM, (ii) pancreatic islet and brain GAD are likely to be cross-reactive, and (iii) the majority of GAD antibodies are directed away from the catalytic site of the brain enzyme. The lower frequency of GAD antibodies in recent-onset IDDM subjects indicates either that immunoreactivity is lost with near-total beta-cell destruction or that GAD antibodies denote a low risk of progression to clinical disease.
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PMID:Glutamic acid decarboxylase autoantibodies in preclinical insulin-dependent diabetes. 140 9

In situ hybridization was used to study the effect of 6-hydroxydopamine-induced damage to the midbrain dopaminergic neurons on the level of glutamate decarboxylase mRNA in globus pallidus neurons in the rat. Some animals received an injection of Fluoro-gold in the entopeduncular nucleus or the substantia nigra prior to the 6-hydroxydopamine lesion in order to identify glutamic acid decarboxylase mRNA levels in pallidal neurons that project to one of these targets. Analysis was carried out on a sample of all pallidal neurons as well as neurons that were identified as projection neurons in control and lesioned groups. The loss of the dopamine-containing neurons in the substantia nigra resulted in significant increases in the percentage of globus pallidus neurons that expressed glutamate decarboxylase mRNA and in the amount of glutamate decarboxylase mRNA per globus pallidus neuron. These increases were noted in a sample of all pallidal neurons, as well as pallidal neurons that were identified as projecting to either the entopeduncular nucleus or the substantia nigra. In control animals, glutamate decarboxylase mRNA was clearly identified in globus pallidus neurons projecting to the entopeduncular nucleus, indicating that this recently reported projection is at least partially GABAergic. The results of this study indicate that substantia nigra dopaminergic neurons regulate globus pallidus neurons in the rat, and that removal of the dopaminergic input to the corpus striatum results in a significant increase in the amount of glutamate decarboxylase mRNA in pallidal neurons. The decreased firing rate of pallidal neurons that is seen following the loss of dopamine input appears to be accompanied by an increase in the level of glutamate decarboxylase mRNA in these neurons.
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PMID:6-Hydroxydopamine lesions of the nigrostriatal pathway alter the expression of glutamate decarboxylase messenger RNA in rat globus pallidus projection neurons. 148 18

Dopaminergic nigrostriatal neurons constitute one of the major inputs to the striatum, and play a role in the regulation of gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD), the GABA-synthesizing enzyme, in striatal neurons. The effect of nigrostriatal lesions on the level of expression of messenger RNAs encoding two distinct isoforms of glutamate decarboxylase was examined at the single cell level with in situ hybridization histochemistry. Rats received a unilateral injection of the neurotoxin 6-hydroxydopamine in the substantia nigra and were sacrificed 2 or 3 weeks later. Sections of the striatum were processed for in situ hybridization histochemistry with radiolabeled RNA probes selective for mRNAs encoding glutamate decarboxylase with molecular weights of 65,000 and 67,000, respectively. In addition, immunohistochemistry with a monospecific antibody for the latter glutamate decarboxylase isoform was performed. In agreement with previous reports, we observed increased labeling for the messenger RNA encoding glutamate decarboxylase (M(r) 67,000) in a population of medium-sized striatal efferent neurons normally expressing low levels of this messenger RNA. We now show that this effect occurred in two striatal compartments, the striosomes and the extrastriosomal matrix, and was accompanied by increased immunostaining for the corresponding protein with a monospecific antibody. In contrast, labeling for messenger RNA encoding GAD (M(r) 67,000) was decreased in a population of medium-sized neurons normally expressing high levels of this messenger RNA and corresponding to GABAergic interneurons. Labeling for messenger RNA encoding glutamate decarboxylase (M(r) 65,000) was not modified in the dopamine-depleted striatum. The results show that dopamine depletion differentially affects gene expression for different isoforms of glutamate decarboxylase in distinct subpopulations of striatal neurons in rat.
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PMID:Messenger RNAs encoding glutamate-decarboxylases are differentially affected by nigrostriatal lesions in subpopulations of striatal neurons. 151 13


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