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

Alterations in gamma-aminobutyric acid (GABA) metabolism have been investigated in the kindling model of epilepsy. Numerous generalized seizures were induced by amygdala-kindling stimulations in rats. One week after the last stimulation, there were no changes in GABA levels nor in the activity of enzymes responsible for the synthesis (glutamic acid decarboxylase) and catabolism (GABA transaminase and succinyl semialdehyde dehydrogenase). These results do not exclude other changes in GABA function as modifications of transport or receptors.
Neurosci Lett 1985 Dec 04
PMID:Absence of modifications in gamma-aminobutyric acid metabolism after repeated generalized seizures in amygdala-kindled rats. 408 36

Brain capillaries (microvessels) were isolated from rabbit brain. Morphological characterization revealed relatively pure fractions of microvessels consisting of the capillary endothelium, the basal membrane, and the pericyte. These fractions of brain capillaries show acetylcholinesterase (AChE) and monoamine oxidase (MAO) activity, but lack catechol-O-methyltransferase and GABA transaminase activity. Isolated brain capillaries together with samples of the brain parenchyma and serum were used to study the role of AChE present in the brain capillary wall in soman intoxication. The results showed this AChE to be less sensitive to soman inhibition than AChE of brain parenchyma. Serum and brain AChE recovered to some extent in soman-intoxicated rabbits given HI-6, whereas AChE present in the microvessel was even further inhibited. It is suggested that soman-induced vasospasm in rabbit brain may explain both the inaccessibility of capillary AChE to soman and also the unfavorable effect of HI-6 on this enzyme.
Fundam Appl Toxicol 1985 Dec
PMID:Soman intoxication and the blood-brain barrier. 409 83

Brain gamma-aminobutyric acid (GABA) has been proposed to play a role in the modulation of extrapyramidal motor function. The effects of increasing brain GABA with gamma-acetylenic GABA (GAG), a drug that inhibits GABA transaminase, were evaluated in ten patients with stable tardive dyskinesia during a blind placebo-controlled trial. Drug effects during active treatment and two placebo periods were evaluated by scoring randomly sequenced videotapes of tardive dyskinesia and parkinsonian symptoms recorded weekly during a standardized examination. Tardive dyskinesia was significantly reduced, and preexisting parkinsonism increased slightly. The largest decrease in tardive dyskinesia symptoms occurred in patients receiving higher neuroleptic doses, suggesting an interaction between GABA and dopamine. Prolactin values increased but growth hormone values were unchanged. Psychiatric symptoms were also unchanged during GAG treatment.
Arch Gen Psychiatry 1980 Dec
PMID:gamma-Acetylenic GABA in tardive dyskinesia. 610 51

2-Aminoethanol (ethanolamine) was studied for effects on neurochemical assays for GABA synthesis, receptor binding, uptake and metabolism in rat brain preparations. The effects of ethanolamine were compared with those of ethanolamine O-sulphate (EOS), an inhibitor of GABA degradation. Furthermore, the effect of both compounds was compared on GABA metabolism in rat brain in vivo. In vitro, ethanolamine and EOS had no significant effect on the GABA synthesizing enzyme glutamic decarboxylase (GAD) and GABA uptake, but both drugs proved virtually equipotent to inhibit the GABA degrading enzyme GABA aminotransferase (GABA-T). EOS was a relatively potent inhibitor of GABA receptor binding, whereas ethanolamine was not effective in this regard. Following systemic administration in rats, 50% inhibition of GABA-T in the brain was achieved by 500 mg/kg ethanolamine or 2000 mg/kg EOS, respectively. As a consequence of GABA-T inhibition, GABA levels increased significantly. GAD activity remained unchanged after both treatments. The present results suggest that the recently reported enhancement of functional effects of GABA by ethanolamine may relate, at least in part, to the inhibitory effect of the compound on GABA catabolism.
Neurosci Lett 1983 Dec 11
PMID:Effect of 2-aminoethanol on the synthesis, binding, uptake and metabolism of GABA. 632 73

The effects of bilateral microinjection of gamma-vinyl GABA (GVG, an irreversible inhibitor of GABA-T) were tested during the development of seizures induced by i.p. administration of 10 mg/kg of kainic acid. Intrahippocampal injection of GVG prevents the development of the seizures at an early stage in about half of the cases. In the remaining animals status epilepticus comparable to that of controls develops. Intra-amygdaloid injection reduces the severity of the seizures from the first motor limbic signs. Finally, intranigral injection prevents the appearance of convulsive status epilepticus or, when it develops, reduces its duration. The role that these three structures could play in the electro-clinical development of kainic acid-induced seizures is discussed.
Rev Electroencephalogr Neurophysiol Clin 1984 Dec
PMID:[Role of the hippocampus, amygdala and the substantia nigra in the evolution of status epilepticus induced by systemic injection of kainic acid in the rat]. 652 78

The reaction of muscimol as amino donor substrate for GABA transaminase (GABA-T) has been studied using enzyme purified from rabbit brain. Enzyme activity was assayed by measuring the glutamate produced using glutamate dehydrogenase. Kinetic parameters determined at 37 degrees C were for GABA, Km (app) = 1.92 +/- 0.24 mM, specific activity = 7.33 +/- 0.27 mumol/min/mg (kcat = 13.7s-1), and for muscimol, Km (app) = 1.27 +/- 0.15 mM, specific activity = 0.101 +/- 0.009 mumol/min/mg (kcat = 0.19s-1). Addition of muscimol to the enzyme caused the spectral changes associated with conversion of the pyridoxaldimine form to the pyridoxamine form, and the first-order rate constant for the reaction showed a dependence on muscimol concentration that followed saturation kinetics, with a K = 1.1 +/- 0.18 mM and kmax = 0.065 +/- 0.004 s-1 (19 degrees C). The rate of spectral change observed on addition of muscimol to ornithine transaminase was extremely slow--at least an order of magnitude slower than that seen with GABA-T.
J Neurochem 1983 Dec
PMID:Reaction of muscimol with 4-aminobutyrate aminotransferase. 664 8

Influences of gamma-butyrolactone (GBL) on GABA agonists-induced gastric acid secretion were studied in anesthetized rats. GBL potentiated the effect of GABA and GABA agonists on gastric acid secretion, and gamma-hydroxybutyric acid, a metabolite of GBL, tended to enhance the effect of GABA. However, GBL did not influence 2-deoxy-D-glucose- or bethanechol-stimulated acid secretion. A benzodiazepine, diazepam, also increased the secretagogue action of baclofen. A GABA antagonist, bicuculline, but not picrotoxin, inhibited the acid secretion stimulated by the combination of GBL and GABA or muscimol. Aminooxyacetic acid, an inhibitor of GABA transaminase, potentiated the effect of GABA. Dopamine receptor agonists and antagonist did not modify the effect of GABA. Neither GABA mimetic action of GBL nor its influences on the dopaminergic system are involved in the effect of the compound on gastric acid secretion. Although the possibility that GBL inhibits GABA degradation is not excluded, the compound appears to increase the sensitivity of GABA receptor to GABA mimetics in the gastric acid secretion.
Jpn J Pharmacol 1983 Dec
PMID:gamma-butyrolactone enhances the activity of GABA in the gastric acid secretion of anesthetized rats. 666 64

Di-n-propylacetate (DPA), aminooxyacetic acid (AOAA), and gabaculine were administered alone or in combination to Swiss mice. Six hours after administration of the drugs the anticonvulsant action (against isonicotinic acid hydrazide-induced seizures) of AOAA and DPA combined was less than that of AOAA alone. The cause of this phenomenon appeared to be an interaction between DPA and AOAA with respect to inhibition of GABA-T activity, resulting in a long-term diminished inhibition by AOAA, which in turn led to a lessening of the AOAA-induced elevation in the GABA content of nerve endings (synaptosomes). An excellent correlation was observed between the delay in onset of seizures and the elevation of synaptosomal GABA content.
J Neurochem 1981 Dec
PMID:Interactions of di-n-propylacetate, gabaculine, and aminooxyacetic acid: anticonvulsant activity and the gamma-aminobutyrate system. 680 Dec 1

The characteristics of accumulation of gamma-aminobutyric acid (GABA) in the retina after an intravitreal injection of the GABA-T inhibitor, gabaculine, have been studied in rats. The accumulation of GABA after injection of gabaculine was both dosage- and time-dependent. In both dark- and light-adapted-retinas. GABA continued to increase linearly for at least 90 min after an injection of gabaculine and this increase (3-fold) was similar in dark- and light-adapted rats. The GABA agonist, muscimol, and the GABA antagonist, bicuculline methiodide, significantly inhibited and facilitated, respectively, the gabaculine-induced increase in GABA levels. Previous studies have shown that accumulation of GABA following the irreversible inhibition of GABA-T was useful for measuring the rate of synthesis of GABA in the central nervous system, and these studies suggest that this technique may also be useful in the retina.
Neuropharmacology 1982 Dec
PMID:The use of gabaculine-induced accumulation of GABA for an index of synthesis of GABA in the retina. 715 8

The effects of gamma-aminobutyric acid (GABA)-alpha-oxoglutarate aminotransferase (GABA-T) inhibitors, L-glutamic acid decarboxylase (GAD) inhibitors, and antipetit mal anticonvulsants on gamma-hydroxybutyric acid (GHB) and GABA were studied. Treatment with anticonvulsants and GABA-T inhibitors resulted in an increase in steady-state brain levels of both GHB and GABA. GAD inhibitors produced markedly decreased levels of brain GABA but no change in GHB concentrations. Studies of GHB derived exclusively from GABA showed that GABA-T inhibitors which produced an elevation of steady-state levels of GHB in brain also resulted in a decrease in GABA-derived GHB. Intracerebroventricular (i.c.v.) administration of GABA, putrescine, and 1,4-butanediol all produced significant elevations in brain GHB, but GABA-T inhibitors blocked this effect of GABA and putrescine. These data suggest that there may be another source for GHB in brain in addition to GABA and raise the possibility that 1,4-butanediol may be that source.
Biochem Pharmacol 1982 Dec 01
PMID:Studies on the relation of gamma-hydroxybutyric acid (GHB) to gamma-aminobutyric acid (GABA). Evidence that GABA is not the sole source for GHB in rat brain. 715 69


<< Previous 1 2 3 4 5 Next >>