Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P80404 (GABA transaminase)
 786 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The administration of L-alpha-amino-beta-chloropropionic acid hydroxamide (L-ACPH) to mice brought about an inhibition in GABA-T activity in the brain of the animals, a significant inhibition occurring with dosage levels as low as 0.25 mmol/kg. Minimum levels of GABA-T activity were reached 3 h after administration of the drug. Brain glutamic acid decarboxylase, DOPA decarboxylase and aspartate aminotransferase activities were not altered by the L-ACPH but alanine aminotransferase activity was totally inhibited. Slight changes in structure caused great changes in the potency of the drugs. For example, the elongation of the L-ACPH structure by one carbon, or a change in the configuration of the amino group from L- to D-, caused a significant decrease in GABA inhibition. The chloro and hydroxamide groups were necessary for inhibitory activity. The administration of L-ACPH to mice delayed the onset of drug induced seizures but had a less noticeable effect against maximal electroshock. The addition of L-ACPH to crude extracts from brain, or to preparations of semipurified GABA-T, also inhibited GABA-T activity. Again the development of the inhibition was time-dependent. Possible mechanisms of action with respect to L-ACPH induced inhibition of GABA-T activity are discussed in the light of the data presented.
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PMID:Alteration of GABA metabolism in mammalian brain by l-alpha-amino-beta-chloropropionic acid hydroxamide and related compounds. 45 23

The effects of administration of DL-penicillamine (PeA), thiosemicarbazide (TSC), semicarbazide-HCl (SC) as convulsants and pyridoxine (PN) as anticonvulsant on gamma-aminobutyric acid (GABA) content, glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid transaminase (GABA-T) activities in cerebral cortex, striatum, diencephalon, mesencephalon, cerebellum and pons/medulla were investigated. The onset of convulsions induced by these convulsants coincides with the fall in GABA content and GAD activity in the mesencephalon area, and in contrast, the cessation of the convulsions by PN supplement coincides with the recovery in both the parameters. Aminooxyacetic acid (AOAA), a potent GABA-elevating agent showed an anticonvulsant property against convulsion by TSC for several hours after the injection of AOAA, but lost this property 16 hr after the treatment. The TSC administration 16 hr after the AOAA pretreatment significantly decreased the GABA content in all the regions, particularly in the mesencephalon and diencephalon areas, which had been elevated by the AOAA pretreatment, together with its ability to induce convulsion. FRom the above results it may be postulated that the critical drop of GABA level from a plateau to another lower level following the decrease of GAD activity in the mesencephalon area is an important factor in the induction of convulsion.
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PMID:Effect of antivitamin B6 on regional GABA metabolism in mouse brain and its relation to convulsions. 54 51

The administration of L-cycloserine to mice resulted in a dramatic decrease in the activities of 4-aminobutyrate:2-oxoglutarate aminotransferase (GABA-T) and L-alanine:2-oxoglutarate aminotransferase (ALA-T) in both brain and liver. L-Aspartate:2-oxoglutarate aminotransferase was inhibited only slightly, and brain glutamic acid decarboxylase not at all. Liver ALA-T activity returned to near normal levels within 24 h of L-cycloserine administration whereas liver GABA-T and brain ALA-T activities had returned only halfway to normal levels in the same time period. The recovery in the activity of brain GABA-T was even slower. A consequence of the inhibition of brain GABA-T activity was an elevation in the GABA content of the tissue which was maximal 3 h after L-cycloserine administration and which was still noticeable 8 h after the drug treatment. L-Cycloserine was also a potent in vitro inhibitor of brain GABA-T activity. The inhibition was competitive with respect to GABA, the Ki value being 3.1 X 10(-5) M. The prior administration of L-cycloserine to mice significantly delayed the onset of isonicotinic acid hydrazide induced convulsions.
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PMID:Effect of L-cycloserine on brain GABA metabolism. 63 58

An isocratic high-performance liquid chromatographic technique was developed to measure levels of gamma-aminobutyric acid (GABA), glutamate, and taurine in the brain and pituitary of goldfish. Accuracy of this procedure for quantification of these compounds was established by evaluating anesthetic and postmortem effects and by selectively manipulating GABA concentrations by intraperitoneal administration of the glutamic acid decarboxylase (GAD) inhibitor 3-mercaptopropionic acid or the GABA transaminase inhibitor gamma-vinyl GABA. The technique provided a simple, rapid, and reliable method for evaluating the concentrations of these amino acids without the use of complex gradient chromatographic systems. To investigate the relationship between neurotransmitter amino acids and the control of pituitary secretion of gonadotropin, the effects of injection of taurine, GABA, or monosodium glutamate on GABA, glutamate, taurine, and, in some instances, monoamine concentrations in the brain and pituitary were evaluated and related to serum gonadotropin levels. Injection of taurine caused an elevation in serum gonadotropin concentrations. In addition, injection of the taurine precursor hypotaurine but not the taurine catabolite isethionic acid elevated serum gonadotropin levels. Intracerebroventricular injection of either GABA or taurine also elevated serum gonadotropin concentrations. Pretreatment of recrudescent fish with alpha-methyl-p-tyrosine reduced pituitary dopamine concentrations and also potentiated the serum gonadotropin response to taurine. Injection of monosodium glutamate caused an increase of glutamate content in the pituitary at 24 h; this was followed by a decrease at 72 h after administration. Pituitary GABA, taurine, and dopamine concentrations underwent a transient depletion after monosodium glutamate administration, and this was associated with an elevation of serum gonadotropin content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amino acid neurotransmitters and dopamine in brain and pituitary of the goldfish: involvement in the regulation of gonadotropin secretion. 134 46

The effects of local anesthetics (procaine and lidocaine) on the gamma-aminobutyric acid (GABA) and L-glutamic acid (Glu) levels in rat spinal cord were studied during the convulsive process. The present study also investigated the influence of central GABA manipulations on the local anesthetic-induced convulsions. An increase in spinal GABA levels was observed at the preconvulsive and convulsive states after administration of procaine (170 mg/kg, i.p.) or lidocaine (120 mg/kg, i.p.), which induced clonic convulsions; in the depressive state, GABA levels returned to normal; in all states, Glu levels were unchanged. Semicarbazide (25-100 mg/kg, i.p.), a glutamic acid decarboxylase inhibitor, produced a decrease in spinal GABA content and strongly enhanced both local anesthetic-induced convulsions as shown by a shortening of the latency and an increase in the mortality. Aminooxyacetic acid (AOAA; 10-40 mg-kg, i.p.), a GABA transaminase inhibitor, dose-dependently increased spinal GABA content and markedly suppressed procaine-induced convulsions. However, lidocaine-induced convulsions were enhanced by AOAA. These results suggest that the spinal GABA neuron may respond to the convulsions induced by local anesthetics. Furthermore, there is a clear relationship between spinal GABA content and procaine-induced, but not lidocaine-induced, convulsions.
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PMID:Some correlations between local anesthetic-induced convulsions and gamma-aminobutyric acid in rat spinal cord. 189 77

The effects of sodium cyanide (NaCN) on the gamma-aminobutyric acid metabolizing enzymes glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid transaminase (GABA-T) were studied in vitro. With no pyridoxal-5-phosphate added, GAD was non-competitively inhibited by NaCN, with an IC50 of 280 microM. GAD was also inhibited when exposed to an equimolar amount of NaCN and pyridoxal-5-phosphate. NaCN inhibited GABA-T. The inhibition kinetics suggests that NaCN may react with more than one of the substrates and products present during the reaction, i.e. pyridoxal-5-phosphate, alpha-ketoglutarate and/or succinic semialdehyde. The presence of pyridoxal-5-phosphate in the reaction mixture completely protected GABA-T from inhibition by NaCN. The gamma-aminobutyric acid synthesizing enzyme, GAD may thus be inhibited in vivo by NaCN or by a reaction product of NaCN and pyridoxal-5-phosphate. The gamma-aminobutyric acid catabolizing enzyme, GABA-T is not as vulnerable to inhibition by NaCN, since the cyanide-pyridoxal-5-phosphate complex is ineffective as inhibitor.
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PMID:On the inhibition of glutamic acid decarboxylase and gamma-aminobutyric acid transaminase by sodium cyanide. 195 76

The presence of GABAergic innervation in cerebral arteries of several species was investigated by an immunohistochemical method using antibodies against glutamic acid decarboxylase (GAD) and GABA transaminase (GABA-T). Both GAD and GABA-T immunoreactivities were found to be associated with large bundles and single fibers in the adventitial layer of arteries examined. The density and distribution pattern of both GAD- and GABA-T-immunoreactive fibers were found to be comparable at most regions examined. Both fibers were found to be most dense in the anterior cerebral artery and its adjacent part of the circle of Willis. Several peripheral arteries were found to receive very sparse or no GAD- and GABA-T-immunoreactive fibers. Superior cervical ganglionectomy did not appreciably affect the distribution of both fibers. Cold-storage denervation, however, resulted in a drastic decrease in both fibers. At ultrastructural levels, both GAD- and GABA-T-immunoreactive nerve profiles were found to be very close to the smooth muscle cells. These results demonstrate the presence of a potentially functional GABAergic innervation in cerebral circulation. On few occasions, GAD immunoreactivities were also found in some endothelial cells, suggesting that a nonneuronal GABA system may also be present in cerebral arteries.
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PMID:GABAergic innervation in cerebral blood vessels: an immunohistochemical demonstration of L-glutamic acid decarboxylase and GABA transaminase. 198 97

(3R,4R),(3S,4S)- and (3R,4S),(3S,4R)-4-amino-5-fluoro-3-phenylpentanoic acid (1a and 1b) were synthesized and studied as selective inactivators of gamma-aminobutyric acid (GABA) aminotransferase. Neither compound caused time-dependent inactivation of the enzyme. Neither compound underwent enzyme-catalyzed transamination nor was fluoride ion eliminated from either compound by the enzyme. No 3-phenyllevulinic acid, the product of elimination of HF followed by enamine hydrolysis, was detected. However, both 1a and 1b were competitive reversible inhibitors of GABA aminotransferase; the Ki for 1a was smaller than the Km for GABA. These results suggest that 1a and 1b bind to the active site of GABA aminotransferase, but gamma-proton removal does not occur. Whereas (S)-4-amino-5-fluoropentanoic acid (AFPA) is a potent inhibitor of L-glutamic acid decarboxylase (GAD), neither 1a nor 1b at concentrations 40 times the Ki of AFPA caused any detectable competitive inhibition of GAD. Therefore, the incorporation of a phenyl substituent at the 3-position of AFPA confirms selective inhibition of GABA aminotransferase over GAD.
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PMID:Selective inhibition of gamma-aminobutyric acid aminotransferase by (3R,4R),(3S,4S)- and (3R,4S),(3S,4R)-4-amino-5-fluoro-3-phenylpentanoic acids. 230 43

The effect of acute and chronic ethanol administration on the level of gamma-aminobutyric acid (GABA), glutamate, aspartate, and glutamine was investigated. The level of GABA rose both after acute and chronic ethanol administration. In chronic experiments also the level of glutamate, aspartate and glutamine were increased. In acute experiments the incorporation from glucose into the studied amino acids (neuronal compartment) increased, while in chronic experiments a decreasing trend was observed. In the glial compartment the incorporation increased only into glutamate and glutamine in acute experiments, while in chronic experiments a decreased incorporation into glutamine was recorded. The activities of three enzymes were studied in seven parts of the brain after acute ethanol administration. The activity of glutamic acid decarboxylase increased in the hypothalamus and brain cortex and decreased in the medulla oblongata. The activity of GABA transaminase did not change and the activity of glutamine synthetase decreased only in the hippocampus. In accordance with several other studies, the presented results show that ethanol interferes with the GABA system in the brain. It is suggested that the primary effect of ethanol is exerted on the cell membranes with preference for the regions connected with the GABA system.
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PMID:[The effect of ethanol on gamma-aminobutyric acid in the brain]. 257 92

By using a radioreceptor assay GABA was detectable in rat interscapular brown adipose tissue (IBAT), the levels being 1% those of CNS and 10-fold those of peripheral plasma. Injection of the glutamic acid decarboxylase (GAD) inhibitor 3-mercaptopropionic acid lowered IBAT GABA levels by about half while injection of the GABA transaminase inhibitor gamma-acetylenic GABA increased them by 230%. Rats kept at 4 degrees C for 14 days exhibited IBAT GABA levels that were about half those found at 22 degrees C. Accumulation of IBAT GABA after gamma-acetylenic GABA increased by 2-fold in cold-exposed rats. Sympathetic denervation of IBAT prevented the effect of the cold environment on GABA content and impaired that on GABA accumulation. GAD activity was detectable in IBAT homogenates and isolated brown adipocytes. Exposure of rats to cold increased Vmax of GAD without modifying its Km, regardless of intactness of innervation. In binding studies with 3H-GABA as a ligand, two types of sites were uncovered of KD = 14 and 146 nM, respectively. In the presence of 2.5 mM Ca2+ bicuculline and baclofen were 57 and 46% as effective as GABA to displace 3H-GABA from IBAT binding sites. The results indicate existence, possible synthesis and type A and B receptors of GABA in rat IBAT.
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PMID:GABA and its neural regulation in rat brown adipose tissue. 275 28


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