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)

Uptake, synthesis, storage, and release of gamma-aminobutyric acid (GABA) are some of the characteristic properties of GABA-ergic neurons. In the present study, we have used these properties as physiological probes to follow the emergence and maturation of GABA-ergic neurons during postnatal development of the rabbit retina. There is autoradiographic, immunocytochemical, and pharmacological evidence that some amacrine cells and certain neurons in the ganglion cell layer probably use GABA as the neurotransmitter. These neurons take up GABA, contain the GABA-synthesizing enzyme L-glutamic acid decarboxylase (GAD, EC 4.1.1.15), and release the accumulated GABA by a CA++-dependent mechanism when depolorized with high extracellular K+ concentration. In this study, we show that certain neurons in the newborn retina already possess a specific mechanism for GABA uptake. The positions and numbers of these cells in the developing retina suggest that they will become GABA-ergic neurons in the adult retina. These putative GABA-ergic neurons are, however, probably immature at birth because newborn retinas contain only low levels of GABA and GAD. Additionally, there is relatively little K+-stimulated, Ca++-dependent release of (3H)-GABA from the newborn retinas. GABA concentrations and GAD activities in developing retinas increase steadily postnatally, reaching about 80% of the adult levels by day 9. The activities of the GABA-degrading enzyme, GABA-glutamate transaminase (GABA-T, EC 2.6.1.19), follow a similar pattern of maturation during retinal development. K+ stimulated GABA release, however, remains low until about day 6, and then increases dramatically from 20% to 85% of the adult level over the next 3 days. Taken together, our results indicate that in the rabbit retina, the commitment by certain neurons to use GABA as the transmitter is made prenatally. These neurons are immature at birth but are biochemically, physiologically, and probably functionally mature by about 9 days after birth.
J Comp Neurol 1980 Sep 01
PMID:Postnatal development of GABA-ergic neurons in the rabbit retina. 625 33

Intraperitoneal injection of ethanol (1-2 g/kg) and chlordiazepoxide (2-16 mg/kg) suppressed susceptibility to audiogenically induced, clonic-tonic seizures and antagonized forelimb tremor in rats undergoing ethanol withdrawal, 30 min after treatment. However, a smaller dose of ethanol (0.5 g/kg) actually increased clonic seizure frequency, suggesting that ethanol exerts a biphasic proconvulsant/anticonvulsant action. Direct activation of gamma-aminobutyric acid (GABA) receptors by intracisternal administration of GABA (100-1000 micrograms), muscimol (0.3-1.0 micrograms) or 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) (0.3-3.0 micrograms) 5 to 10 min before testing also reduced susceptibility to audiogenic clonic-tonic seizures. In sharp contrast to these anticonvulsant actions, GABA, muscimol and THIP had no effect on withdrawal-induced forelimb tremors. Blockade of GABA uptake with 1-2,4-diaminobutyric acid (300 and 600 mg/kg i.p.) and inhibition of GABA transaminase with aminooxyacetic acid (12.5 and 25.0 mg/kg i.p.) both reduced susceptibility to seizures. However, anticonvulsant doses of these two drugs, unlike GABA, muscimol and THIP, also reduced forelimb tremor. Three other GABA transaminase inhibitors, gamma-vinyl GABA (450 and 900 mg/kg i.p.), gamma-acetylenic GABA (50-150 mg/kg i.p.) and ethanolamine-O-sulfate (250-750 mg/kg i.p.), were inactive against ethanol withdrawal audiogenic seizures and forelimb tremors. These results indicate that direct GABA receptor activation can selectively suppress one type of ethanol withdrawal response (i.e., audiogenic seizure susceptibility) while failing to influence another (forelimb tremors).
J Pharmacol Exp Ther 1983 Sep
PMID:Differential sensitivity of ethanol withdrawal signs in the rat to gamma-aminobutyric acid (GABA)mimetics: blockade of audiogenic seizures but not forelimb tremors. 631 80

We studied the effects of microinjected drugs and brainstem lesions on motor and limbic seizures in the kindling model of epilepsy. The duration of motor seizures was determined by timing the colonic and tonic movements of the extremities. The duration of limbic seizures was determined by measuring afterdischarge recorded on the electroencephalogram. Bilateral microinjection of a gamma-aminobutyric acid (GABA) agonist, muscimol, into the area of the substantia nigra (SN) markedly suppressed both motor and limbic seizures induced by stimulation of amygdala, olfactory structures, or lateral entorhinal cortex. Microinjection of saline did not suppress seizures. The suppressive effect of muscimol: (i) dissipated after several hours and was dependent on dose; (ii) was due to an elevation of the seizure threshold, since typical seizures could be elicited with electrical current far exceeding the threshold; and (iii) exhibited spatial specificity since muscimol injections 1 to 2 mm dorsal to the SN or into neocortex did not suppress the seizures. The actions of muscimol were probably mediated by its GABA agonist properties, since microinjection of an irreversible inhibitor of GABA transaminase (gamma-vinyl GABA) into the area of the SN also suppressed kindled seizures. Destruction of brainstem structures was produced by microinjection of the neurotoxin, N-methyl-D,L-aspartate. Seizures were markedly suppressed in animals with bilateral destruction of the SN but not in animals in which the SN was spared bilaterally. We interpret the data to indicate that the SN is the site at which the GABA agonists and lesions act to raise the threshold for kindled seizures. The suppression of limbic seizures indicates that this brainstem nucleus can regulate the intrinsic neuronal excitability of hemispheric sites.
J Neurosci 1984 Sep
PMID:Evidence implicating substantia nigra in regulation of kindled seizure threshold. 648 54

Succinic semialdehyde dehydrogenase deficiency has been demonstrated in a fourth patient with 4-hydroxybutyric aciduria. Lysates of freshly isolated lymphocytes and cultured lymphoblasts of the patient had much lower than control activity in the conversion of U-14C-4-aminobutyric acid to 14C-succinic acid in an assay designed to estimate succinic semialdehyde dehydrogenase utilizing endogenous 4-aminobutyrate transaminase. Lymphocyte and lymphoblast lysates of the patient accumulated U-14C-succinic semialdehyde when incubated with U-14C-4-aminobutyric acid and NAD+ whereas none could be detected in controls. Assays using U-14C-succinic semialdehyde as substrate for succinic semialdehyde dehydrogenase in lysates of cultured lymphoblasts characterized the patient as having a severe deficiency of succinic semialdehyde dehydrogenase. The data indicate that defective activity of succinic semialdehyde dehydrogenase is responsible for 4-hydroxybutyric aciduria.
Eur J Pediatr 1984 Sep
PMID:Defective succinic semialdehyde dehydrogenase activity in 4-hydroxybutyric aciduria. 648 77

4-aminobutyrate-2-oxoglutarate aminotransferase (GABA-T) has been found in adrenal medulla. The enzyme from this tissue is very similar to those found in other tissues in respect to their mitochondrial localization, optima pH and responses to cofactor. The enzyme from medulla has substrate km values similar to those for the brain enzyme, while it differs from those found for other tissues such as kidney, liver and platelets.
Rev Esp Fisiol 1983 Sep
PMID:GABA-T in bovine medulla cells: kinetic properties and comparison with GABA-T from other tissues. 665 45

The effect of di-n-propylacetic acid (valproic acid), a gamma-aminobutyric acid transaminase inhibitor, on the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response to gonadotropin-releasing hormone (LHRH) was studied in five normal women during the proliferative and luteal phases of the menstrual cycle. Valproic acid produced no significant change in the basal serum concentrations of LH, FSH, estradiol, and progesterone in either the proliferative or the luteal phase of the study. In the proliferative phase the delta LH (maximum increment above baseline) following LHRH stimulation rose from 32.8 +/- 21.2 (mean +/- SD) to 52.2 +/- 28.7 mlU/ml (not significant) after valproic acid, while the delta FSH rose from 2.2 +/- 1.1 to 5.0 +/- 3.6 mlU/ml (not significant). Four of the five volunteers showed an augmentation of the delta LH response to LHRH after valproic acid while the fifth subject showed no change. In three subjects the augmented delta LH response after valproic acid was highly significant. By contrast, the delta LH in the luteal phase following LHRH stimulation fell from 65.3 +/- 20.1 to 43.1 +/- 12.9 mlU/ml after valproic acid (p less than 0.03). Corresponding delta FSH values were 2.5 +/- 1.1 and 2.1 +/- 0.8 mlU/ml (not significant). It is speculated that gamma-aminobutyric acid may exert a modulatory role on gonadotropin secretion following LHRH stimulation and that this effect is influenced by the phase of the menstrual cycle.
Am J Obstet Gynecol 1982 Sep 01
PMID:A presumptive role for gamma-aminobutyric acid in the regulation of gonadotropin secretion in man. 681 Jun 97

It has been reported in several recent studies that the manipulation of cerebral 4-aminobutyric acid (GABA) level results in unexpected changes in the cerebral polyamine metabolism in vivo. The mechanisms behind these interactions have remained unknown. The present results show that the changes in polyamine metabolism are not limited to the brain, but are observable also in the liver, which served as a peripheral reference tissue. Different types of responses in the activities of the polyamine-synthesizing enzymes, ornithine decarboxylase and adenosylmethionine decarboxylase, were observed after increasing the cerebral GABA concentration of mice with varying doses of two GABA transaminase inhibitors, gabaculine and ethanolamine-O-sulphate. The time course of the significant changes in the enzyme activities showed significant correlation between the brain and liver. The possibility of direct effects of the drugs on liver was excluded by injecting them intracerebroventricularly, and by performing control experiments with equal doses given peripherally. It is concluded that the observed changes in the polyamine metabolism of liver are produced through centrally mediated humoral regulation, and that the corresponding changes in the brain are obviously due to the same factor or factors, since they are significantly correlated to the changes in liver.
J Neurochem 1983 Sep
PMID:Possible involvement of humoral regulation in the effects of elevated cerebral 4-aminobutyric acid levels on the polyamine metabolism in brain. 687 58

The rate of cortical gamma-aminobutyric acid (GABA) turnover was estimated by determining the rate of GABA accumulation following inhibition of GABA transaminase by gamma-vinyl-GABA (1.5 g/kg, i.v.) in paralysed, ventilated rats. During 1 h of bicuculline-induced seizures (1.2 mg/kg, i.v.) the rate of accumulation of cortical GABA level is approximately threefold greater than in the control group receiving gamma-vinyl-GABA alone, suggesting that the GABA shunt activity increases in parallel with the increase in overall cortical metabolic rate observed during bicuculline seizures. Pretreatment with gamma-vinyl-GABA did not affect the bicuculline-induced changes in other major cortical amino acids.
J Neurochem 1983 Sep
PMID:Cortical GABA turnover during bicuculline seizures in rats. 687 71

In young chicks the effects of two different doses of apomorphine, a small dose, producing behavioural and electrocortical sleep and a larger one producing arousal, on GABA content, GAD and GABA-T activities in the paleostriatum augmentatum were studied. The small dose of apomorphine did not affect GABAergic mechanisms in this area, whereas the dose producing behavioural and electrocortical arousal significantly increased GAD activity and GABA content. The results of the present experiments are in favour of an interaction between dopaminergic and GABAergic mechanisms in the avian paleostriatum augmentatum.
Neuropharmacology 1982 Sep
PMID:Effects of apomorphine on glutamate decarboxylase activity in chick paleostriatum augmentatum. 714 38

The GABA system was studied in different regions of the rat's brain following inhibition of brain GABA catabolism with intracisternal ethanolamine-O-sulphate or intraperitoneal aminooxyacetic acid. Both treatments lowered GABA aminotransferase and glutamate decarboxylase activities to similar extents in equivalent nuclei on either side of the brain. However, GABA contents were elevates to a consistently higher level in the right-hand substantia nigra, superior colliculus and nucleus accumbens, and in the left-hand ventral tegmentum, ventromedial thalamus and caudate nucleus, with no bilateral asymmetry evident in globus pallidus. These findings are discussed with reference to possible inherent inequalities in the functional states similar GABA systems on opposite sides of the brain.
Neurosci Lett 1981 Sep 01
PMID:Bilateral asymmetry in brain GABA function? 727 13


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