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At least 649 records · Page 36Linked to original sources
PubMed1998

Effects of phenelzine and imipramine on the steady-state levels of mRNAs that encode glutamic acid decarboxylase (GAD67 and GAD65), the GABA transporter GAT-1 and GABA transaminase in rat cortex.

There is an increasing body of evidence suggesting that GABA plays an important role in the therapeutic effects of antidepressant/antipanic drugs. Phenelzine and imipramine are efficacious in the treatment of depression and panic disorder and phenelzine has been reported to elevate GABA levels while imipramine enhances GABA release in rat brains. In the present study, using a multiprobe quantitative solution hybridization assay, we measured the steady-state levels of mRNAs that encode glutamic acid decarboxylase (GAD67 and GAD65), the GABA transporter GAT-1 and GABA transaminase (GABA-T) in rat cortex after treatment with constant infusion (via osmotic minipumps) of phenelzine or imipramine for a short-term (3 days) or long-term (21 days) period. We found that none of the treatments gave rise to significant changes in the steady-state levels of mRNAs encoding GAD67, GAD65 or GABA-T at any time point. The steady-state levels of GAT-1 mRNA were increased significantly (23%) after long-term, but not by short-term, treatment with phenelzine. Imipramine treatment, short- or long-term, did not alter the steady-state levels of GAT-1 mRNA. These results suggest that the GABA enhancing effects of phenelzine or imipramine in rat cortex do not affect the steady-state levels of mRNAs that encode GAD67, GAD65 and GABA-T. Further, the previously observed increases in GABA levels or GABA release induced by these drugs are probably not a consequence of changes in the expression of these genes.

4-Aminobutyrate Transaminase↗
PubMedDate not supplied

Glutamine transaminase K intranephron localization in rats determined by urinary excretion after treatment with segment-specific nephrotoxicants.

Glutamine transaminase K(GTK) excretion assessed in urine and by kidney histology was evaluated in rats after single treatment with 1.0 mg/kg i.p. of mercuric chloride, 100 mg/kg i.p. of hexachloro-1:3-butadiene (both S3, pars recta, segment-specific nephrotoxicants) and 25 mg/kg s.c. of potassium dichromate (S1-S2, pars convoluta, segment-specific nephrotoxicant). The aim was to correlate segment-specific injury and enzyme excretion in order to assess, using non-vasive methods, localization of GTK along the proximal tubule. Mercuric chloride and hexachloro-1:3-butadiene produced early focal damage in the pars recta (focal necrosis was shown 10 h after treatment, and diffuse necrosis appeared later at 34 and 24 h after treatment). Changes of the pars convoluta were occasional and delayed (72 h after treatment for both substances). On the contrary, potassium dichromate induced damage of the pars convoluta (vacuolar degeneration and focal necrosis were evident 24 h and 48 h after treatment, respectively), whereas the pars recta was affected later (focal vacuolar degeneration was observed 72 h after treatment). Increase urinary GTK excretion was early after treatment with mercuric chloride and hexachloro-1:3-butadiene (significant increase was observed within 10 h), with a peak for both substances 24 h after treatment, in agreement with the necrosis of the pars recta. Potassium dichromate induced a significant increase of enzyme excretion in urine also 24 h after injection, according to histological features showing vacuolar degeneration of the pars convoluta; the peak of excretion was reached 48 h after treatment (delay was due, probably, to s.c. administration). The results show that GTK increased in urine after treatment with S3 and S1-S2 specific nephrotoxicants; the combination of histological examination and urinary enzyme supports the evidence that the enzyme is distributed along the whole of the proximal tubule.

Animals↗
PubMed1999

Effects of GABA-transaminase inhibition on brain metabolism and amino-acid compartmentation: an in vivo study by 2D 1H-NMR spectroscopy coupled with microdialysis.

The aim of this work was to study the neurochemical effects in the brain of GABA-transaminase inhibition by systemic administration of gabaculine (100 mg/kg, i.a.) in the rat. In order to investigate neurotransmitter and related amino-acid compartmentation and metabolism, we have developed an original tool: the coupling, in vivo, on the same animal, of 2D COSY 1H-NMR spectroscopy with intracerebral microdialysis. The main result is a continuous increase in GABA levels, both in the intracellular compartment (up to 3000+/-450%; P<0.001) and extracellular compartment (up to 808+/-82%; P<0.01) at the sixth hour. The intracellular increase in GABA level became significant at the first hour following gabaculine administration, whereas the extracellular level increased as of the second hour, probably indicating that accumulation of GABA in nerve endings precedes its release in synaptic clefts. Moreover, the levels of the excitatory amino acids, glutamate and aspartate, were decreased both in the intra- and extracellular compartments, thus enhancing sedative effects of the drug. We also observed a decrease in the global energetic creatine-phosphocreatine pool, which also could be related to the sedative properties of gabaculine, measurable by the diminution of cortical electrical activity and mean arterial blood pressure. Finally, the coupling between 2D 1H-NMR spectroscopy and intracerebral microdialysis appears to be an original tool for investigating the cerebral metabolic effects induced by pharmacological agents, in situ, in living animals.

4-Aminobutyrate Transaminase↗
PubMed2006

Molecular cloning and differential expression of an gamma-aminobutyrate transaminase gene, OsGABA-T, in rice (Oryza sativa) leaves infected with blast fungus.

gamma-Aminobutyrate transaminase (GABA-T) catalyzes the conversion of GABA to succinic semialdehyde. Using differential display PCR and cDNA library screening, a full-length GABA-T cDNA (OsGABA-T) was isolated from rice (Oryza sativa) leaves infected with an incompatible race of Magnaporthe grisea. The deduced amino acid sequence comprises 483 amino acid residues and shares 85-69% identity with GABA-T sequences from other plants. OsGABA-T expression is induced by blast fungus infection, mechanical wounding and ultraviolet radiation in rice leaves and is not detected in normal rice organs. This gene is also induced by defense signal molecules such as salicylic acid and abscisic acid, but not by jasmonic acid. Our data suggest that OsGABA-T (GABA shunt) may play a role in restricting the levels of cell death during the host-pathogen interaction.

4-Aminobutyrate Transaminase↗
PubMed1987

Ketimine rings: useful detectors of enzymatic activities in solution and on polyacrylamide gel. Detection of L-amino acid oxidase, glutamine transaminase, pantetheinase, and acylase I.

A simple procedure has been developed for the detection of L-amino acid oxidase, glutamine transaminase, pantetheinase, and acylase I in solution and on polyacrylamide gels. The method is based on the strong absorbance at 296 nm of some ketimine rings which can be directly produced by the enzymatic reaction or formed by the reaction of the enzymatic product with 3-bromopyruvate. The procedure allows one to visualize up to about 1-10 mU of enzyme.

Amidohydrolases↗
PubMed1976

Resolution and complementation of the labile L-leucine-pyruvate transaminase. An intermediate during enzyme formation under nitrogen starvation in Gluconobacter suboxydans.

L-Leucine-pyruvate transaminase (mol. wt. 70 000) in Gluconobactersuboxydans synthesized during nitrogen starvation contained a labile form which changed to the stable one later. The labile enzyme (mol. wt. 70 000) dissocated to the two proteinaceous components: a cationic one (mol. wt. 10 000--20 000) and an anionic one (mol. wt. 50 000--60 000), during column chromatography on DEAE-cellulose. The enzyme activity was reconstructed when they were mixed. The reconstructed enzyme had almost the same molecular size and enzymatic properties as the labile and the native stable enzymes.

Drug Stability↗
PubMed1984

Chronic administration of the GABA-transaminase inhibitor ethanolamine O-sulphate leads to up-regulation of GABA binding sites.

In rats receiving the gamma-aminobutyric acid (GABA)-transaminase inhibitor ethanolamine O-sulphate (EOS) in their drinking water for up to 28 days, the number of GABAA and GABAB binding sites was increased compared to controls. There was no change in binding affinity at GABAA or GABAB sites. One week after EOS withdrawal, the number of GABAA and GABAAB sites in previously treated EOS rats did not differ from controls. There was no difference in the number or affinity of benzodiazepine binding sites between EOS-treated and control rats during EOS administration or withdrawal. There was no difference in the stimulation of benzodiazepine binding by GABA (alone or in the presence of NaCl) during EOS administration. Cortical and cerebellar GABA concentration was increased 3.2- to 4.6-fold and cortical glutamate decarboxylase (GAD) activity reduced 30-42%. The current required to induce electroshock convulsions did not differ between EOS-treated rats and control rats during EOS administration. We speculate that the stimulus for the increased number of GABAA and GABAB binding sites is a reduction in GABA release subsequent to a reduction in GAD activity.

4-Aminobutyrate Transaminase↗
PubMed1985

Effects of inhibitors of GABA-transaminase on hole-board exploration and on temperature. Relation with effects on quasi-morphine abstinence behaviour induced by sodium dipropylacetate.

Four inhibitors of gamma-aminobutyric acid transaminase (GABA-T) were investigated together with respect to their effects on hole-board exploration and temperature and the relation with effects on quasi-morphine-abstinence behaviour induced by dipropylacetate (DPA) in rats. Amino-oxyacetic acid (AOAA), gamma-acetylenic-GABA (GAG), gamma-vinyl-GABA (GVC) and ethanolamine-O-sulfate (EOS) were found to reduce hole-board exploration especially in the higher doses used, although the time-course of the effect was different for the compounds. For EOS and GVG the decrease in hole-board exploration paralleled a strong hypothermic effect. The compounds AOAA and GAG exerted a less and more transient hypothermic effect. However, the decrease in hole-board exploration did not fall in with this decrease in temperature. AOAA and GAG were found to decrease DPA-induced body shakes and locomotor activity, while GVG and EOS had no effect on body shakes and transient effects but opposite to each other, on locomotor activity. The efficacy of the GABA-T-inhibitors was measured biochemically, and the influence on the activity of glutamate decarboxylase (GAD) was also determined. AOAA and GAG were found to be strong inhibitors of GABA-T whereas the other two compounds were less efficient in the used doses. In addition AOAA and GAG influenced the activity of GAD strongly, while using GVG only a small decrease was found. The results suggest that the anti-quasi-withdrawal, the sedative and the hypothermic effects are not related to each other nor related to an effect on GABA-T. The suppressive effects on quasi-withdrawal body shakes, however, could be related to the inhibition of GAD and a hypothesis involving a compartmentalized action of DPA on GABA-metabolism has been proposed.

4-Aminobutyrate Transaminase↗
PubMed1984

Retrograde HRP tracing combined with a pharmacohistochemical method for GABA transaminase for the identification of presumptive GABAergic projections to the habenula.

A pharmacohistochemical method for GABA-transaminase (GABA-T), the key enzyme for GABA metabolism, has been combined with retrograde tracing by horseradish peroxidase, to a study of projections to the lateral habenula. The results indicate that projections to the lateral habenula arise from both GABA-T intensive and non-GABA-T staining cells in the rostral entopeduncular nucleus and the lateral hypothalamus suggesting that these projections contain GABAergic elements, as indicated by previous work, but also involve other neurotransmitters. A few GABA-T intensive cells in the lateral preoptic area were also found to project to the lateral habenula by this double staining technique.

4-Aminobutyrate Transaminase↗
PubMed1984

Quantitative histochemical measurement of GABA-transaminase: method for evaluation of intracerebral lesions produced by excitotoxic agents.

GABA-transaminase (GABA-T) activity of fresh frozen coronal sections through rat striatum was evaluated 4-6 weeks after intrastriatal application of kainic or ibotenic acid. 16 micrograms sections were processed for GABA-T histochemistry and were evaluated quantitatively by computerized densitometry using image analysis. Alternate sections (200 micrograms) were assayed for GABA-T activity in vitro. Gross examination of sections stained for GABA-T revealed obvious lack of staining in the vicinity of lesions produced by either kainate (0.5-1.0 micrograms) or ibotenate (10-20 micrograms); the extent of each lesion was clearly delineated by the stain. Quantitative analysis of stained sections revealed that the lesioned tissue contained 80-90% less GABA-T activity than control tissue. This loss of GABA-T was in agreement with values obtained in adjacent sections assayed in vitro. Similar studies in substantia nigra clearly and quantitatively demonstrated damage induced by ibotenate or kainate in this nucleus as well as in tissue in the overlying reticular formation. Moreover, two compartments of GABA-T were discriminated in substantia nigra: one associated with neural perikarya, which was sensitive to kainic and ibotenic acids (80% of total GABA-T), and a second associated with afferent terminals arising from forebrain projections (20%). Thus, after destruction of neurons with kainic or ibotenic acid, GABA-T activity is largely eliminated. Under these conditions, it appears that glia contribute relatively little to the GABA-T activity measured either histochemically or by direct chemical assay in homogenates.

4-Aminobutyrate Transaminase↗
PubMed1985

Striatonigral and pallidonigral pathways studied by a combination of retrograde horseradish peroxidase tracing and a pharmacohistochemical method for gamma-aminobutyric acid transaminase.

The pharmacohistochemical neuronal staining method for gamma-aminobutyric transaminase (GABA-T) combined with retrograde horseradish peroxidase (HRP) staining was used to define more precisely the descending striatonigral and pallidonigral pathways. Previous studies have established that GABA-T intensive cells in the basal ganglia and other structures correspond with reported glutamic acid decarboxylase (GAD)-containing cells and are therefore presumed to use GABA as their neurotransmitter. Following injection of HRP into the substantia nigra, many HRP-labeled cells were detected in the caudate-putamen and globus pallidus. Two separate groups of cells were doubly labeled for GABA-T and HRP and seemed to represent two distinct GABA-T-rich descending pathways to the substantia nigra. One component came from medium-sized cells in the lateral aspect of the globus pallidus. It represented a majority of all descending cells from that nucleus. The other came from the lateral aspect of the caudate-putamen and represented only a minority of descending cells from that structure. These data suggest that the majority of striatonigral fibers are non-GABA containing while the majority of pallidonigral fibers are GABA-containing. The precise location of the GABA-T intensive cells making up these two pathways helps to explain much confusing data in the literature on the source of descending GABA fibers to the substantia nigra.

4-Aminobutyrate Transaminase↗
PubMed1985

Iron concentration reduced in ventral pallidum, globus pallidus, and substantia nigra by GABA-transaminase inhibitor, gamma-vinyl GABA.

Recent histochemical studies indicate that there is considerable overlap of brain areas accumulating iron in oligodendrocytes with those in which GABA neurons terminate. The ventral pallidum, globus pallidus, substantia nigra and cerebellar nuclei are iron-rich areas, receive GABA-containing efferents, and have high concentrations of gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD). The present study examines the effect of disruption of the metabolism of GABA on the accumulation of iron in GABAergic projection sites. Gamma-vinyl GABA, an enzyme activated inhibitor of GABA-transaminase, was injected unilaterally into the globus pallidus and adjacent striatum or into the substantia nigra of the rat brain. Additional animals received unilateral injections of saline into the same areas or an electrocoagulation lesion of the globus pallidus and surrounding striatum. Two days after injection or lesion all animals were perfused and 40 micron sections of the brain were processed with the Perls' + diaminobenzidine (DAB) histochemical method for iron. The intensity of iron stain was measured with densitometry. Gamma-vinyl GABA injection into the striatum/pallidum resulted in a significant reduction in iron concentration in the ipsilateral ventral pallidum, globus pallidus and substantia nigra. Gamma-vinyl GABA injected into the substantia nigra reduced iron in the injection site. This study provides evidence that the presence of iron in the brain is related to the utilization of GABA.

4-Aminobutyrate Transaminase↗
PubMed1986

Retardation of resynthesis of GABA-transaminase in some brain regions of amygdala-kindled rats.

The activities of GABA-transaminase (GABA-T) were examined in several brain regions of amygdala-kindled rats, pretreated either with or without gabaculine, an irreversible GABA-T inhibitor. Histochemical and biochemical studies demonstrated that GABA-T activities decreased significantly in some brain regions 16 h after the gabaculine treatment. In contrast, no such alteration was detected in kindled animals after a 48-h survival period either with or without the pharmacological manipulation. The present results suggest that kindling causes retardation of GABA-T resynthesis in neurons, since the GABA-T activities detected 16 h after the drug treatment are due to newly synthetized enzyme in presumptive GABA neurons but not glial cells.

4-Aminobutyrate Transaminase↗
PubMed1987

The effects of in vivo inactivation of GABA-transaminase and glutamic acid decarboxylase on levels of GABA in the rat retina.

Gabaculine and gamma-vinyl GABA (GVG) are specific enzyme-activated irreversible inhibitors of GABA-transaminase (GABA-T). gamma-Acetylenic GABA (GAG) irreversibly inhibits both GABA-T and glutamic acid decarboxylase (GAD). Subcutaneous injection of any of those compounds rapidly elevated levels of GABA in the retinae of rats. After injection of 10 mg/kg gabaculine, levels of retinal GABA climbed 5-fold in 4 h, and peaked 16 h after injection at levels approximately 7 times those from water-injected control rats. They remained significantly elevated compared to control levels for at least 6 days after injection. The postgabaculine increase in levels of retinal GABA was linear with time between 0.5 and 4 h after injection. In contrast, retinal GABA levels peaked at less than 3 times control levels within 8 h of injection of 50 mg/kg GAG and returned to baseline levels within 4 days. GAG, upon coadministration with gabaculine, significantly attenuated the postgabaculine rise in levels of GABA in retinae. Neither the rate of rise, nor the maximum levels, of retinal GABA was so great after injection of GAG plus gabaculine, compared to those after injection of gabaculine alone. The degree to which postgabaculine GABA accumulation was inhibited in the retina by 50 mg/kg GAG closely corresponded with the extent to which that dose of GAG inactivated retinal GAD activity. The results of this study extend previous reports from this laboratory that systemically administered gabaculine, GVG and GAG all inactivate target enzymes more potently in retina than in other brain regions.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminobutyrate Transaminase↗
PubMed1984

Hexadeoxycycloheptaamylose-pyridoxamine, an artificial transaminase with a "deeper" binding pocket.

Cycloheptaamylose was converted in four steps into a monosulfonylated, hexadeoxy derivative that, on treatment with pyridoxaminethiol, provided an artificial transaminase with activity similar to that found in the nondeoxygenated analogue. Characterization of the intermediate hexadeoxycycloheptaamylose was facilitated by the use of field-desorption mass spectrometry, which was uniquely able to distinguish between penta-, hexa-, and hepta-deoxycycloheptaamylose. A detailed description of experimental methods for the first time makes this modified binding-site available for general use in the design of enzyme mimics.

Amylose↗
PubMed1978

Demonstration of antibody for glutamic pyruvic transaminase (GPT) in chronic hepatic disorders.

The present paper describes the detection of an autoantibody for glutamic pyruvic transaminase (GPT) in sera of patients with chronic hepatic disorders. In 16 out of 500 patients, the existence of an antibody for pig GPT was demonstrated by the double antibody method, gel filtration and radioimmunoelectrophoresis. The antibody was demonstrated as an immunoglobulin G (IgG) with either polyclonal or monoclonal type (kappa or lambda). The binding portion of IgG with GPT was determined as the fragment Fab, but not Fc of IgG. Because the binding of 125I-pig GPT with the patient's antibody was displaced by human GPT, this antibody may have the characteristic of cross reacting with both pig and human GPT. Although the mechanism of production of the antibody for GPT and the pathological significance of the antibody in chronic hepatic disorders remained obscure, possible inhibition of GPT activity in serum is suggested in the presence of this antibody.

Alanine Transaminase↗
PubMed1995

Basic aspects of GABA-transaminase in neuropsychiatric disorders.

Over the last two decades, there have been several studies suggesting the major inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) is involved directly and/or indirectly in the pathogenesis of many neurologic diseases and psychiatric disorders. GABA is mainly degradated to succinic semialdehyde in a reaction catalyzed by the enzyme GABA-transaminase (GABA-T). Inhibition of this enzyme produces considerable elevation of GABA contents in the brain, and such elevation has been found to correlate with pharmacologic and behavioral effects. We focus attention, from the basic aspects, on brain and platelet GABA-T activities in various species, with a special reference to neuropsychiatric disorders. It seems that the activity of GABA-T in the brain and/or in the blood platelets is correlated to certain neuropsychiatric disorders such as alcoholism, epilepsy, and Alzheimer's disease. In animal and human studies, platelet GABA-T was identified with similar kinetic and inhibitor characteristics to those of the brain. Therefore, in this way, studies of the activity of the enzyme GABA-T in relation to neuropsychiatric disorders could be undertaken to understand, diagnose, and treat GABA-related disorders of the central nervous system.

4-Aminobutyrate Transaminase↗
PubMed1985

Evidence of hemin as an end product inhibitor of L-alanine: 4,5-dioxovalerate transaminase in rat liver mitochondria.

This study describes the in vitro and in vivo effect of hemin on L-alanine:4,5-dioxovalerate transaminase activity. Hemin was shown to be an inhibitor of the purified enzyme and this inhibition was proportional to the concentration of hemin. The examined kinetic data with hemin showed uncompetitive inhibition for both alanine and 4,5-dioxovalerate. An apparent Ki of 30 and 42 microM for hemin were obtained with both alanine and 4,5-dioxovalerate, respectively. Moreover, the enzyme activity in liver was considerably decreased after the intravenous hemin administration and such an inhibition is dose and time dependent. Furthermore, maximum inhibition of the enzyme was observed 30 min after hemin injection and 60% enzyme inhibition was achieved with a dose of 1.2 mg/kg body wt of rat. Thus is suggests the important role of this enzyme on heme biosynthesis.

Alanine↗