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)

Our efforts have been directed towards characterizing amino acid uptake, metabolism and release in bulk-isolated glia and neuronal perikarya studied in parallel with nerve-endings, especially as it concerns the transmitter amino acids and the participation of glia in the clearing of the synpatic space during impulse conduction. A possible neuromodulator role for the glia at the synapse is also suggested by K+-stimulated release. Our most definitive conclusions have been based so far on studies with GABA, although we are also beginning to accumulate data for glutamate related to glutamate-glutamine compartmentation. Glia preferentially accumulate potassium and amino acids compared to neuronal perikarya, have higher Na+/K+-ATPase activity, possess high-affinity, sodium-dependent uptake systems for GABA and glutamate similar to the ones in synaptosomes, and release amino acid in response to a potassium pulse by a calcium-independent process. Low neuronal uptake could be due to loss of dendrites. Unidirectional GABA-flux from the synaptosomal to glial compartment is supported by high GAD in nerve endings compared to high GABA-T in glia. Glutamine may be a transmitter glutamate-precursor in nerve-endings since glutaminase activity is high in nerve-endings, but low in glia where glutamine is presumably made. Glutamine uptake in both glia and synaptosomes obeys low-affinity kinetics in contrast to glutamate, consistent with the inability of glutamine to excite the neuronal membrane. The studies with GABA, which are considerably more extensive, are supported by related work using glia in tissue-culture and autoradiography. There appears to be a suggested difference in the behavior of amines which were poorly taken up by the glial system. Glia, synaptosomes and neuronal perikarya, in general behaved similarly with respect to requirements for uptake and release, except in the case of Ca++, which exerted opposite effects on glial and synaptosomal uptake of GABA. We believe that work along these lines tends to firmly establish a direct role for glial cells as modulators of neuronal excitability and represents a convergence between transmitter amino acid neuropharmacology and cellular biochemistry. This not only deepens and enlarges the vocabulary of synaptic biochemistry but also undoubtedly will have major clinical applications in the fields of epilepsy and behavior.
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PMID:Amino acid transport in isolated neurons and glia. 0 26

Regional brain GABA distribution studies show that after administration of sodium n dipropylacetate, a competitive inhibitor of GABA transaminase, the concentration of GABA increases in some regions i.e. Olfactory Bulbs, Hypothalamus, Cortex, Cerebellum. The GABA level remains unchanged in Caudate Nucleus, Pons Medulla, Hippocampus in our experimental conditions. These variations do not correlate with the initial GABA level.
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PMID:[Effects of sodium n-dipropylacetate on the GABA level in various areas of the mouse brain]. 14 Jul 50

An elevation in cerebral GABA level (65%) is observed after administration of an anticonvulsant, sodium propyl 2-pentene-2 oate, a branched chain fatty acid, comformationally restricted GABA analogue, competitive inhibitor of GABA-T in regard to GABA. The concentration of GABA increases in some regions i.e. substantia nigra, frontal and temporal cortex, cerebellum and olfactory bulbs. The GABA level remains unchanged in caudate nucleus, hippocampus and occipital cortex. Results are discussed comparatively to the effect of sodium n-dipropylacetate.
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PMID:[Effect of propyl-2-pentene-2-oic acid on GABA levels in different regions of mouse brain]. 15 51

The effect of sodium n dipropylacetate (nDPA), a competitive GABA-T inhibitor with respect to GABA, has been investigated on glial and neuronal cellular GABA level. After 1 to 4 days incubation with nDPA in the culture medium, a decrease of GABA level in M5 neuroblastoma clonal cell lines and no modification of GABA level in C6 astrocytoma cells has been observed. The combined addition of nDPA 4 micrometer with dibutyryl cyclic AMP (1 mM) to the culture medium induces the same decrease in GABA level in C6 astrocytoma cells as the addition of DB-c-AMP alone. After shorter incubation time with nDPA (5-150 min), we observed a decreased GABA level in C6 astrocytoma glial cells.
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PMID:[Effect of sodium n-dipropylacetate (sodium valproate) on GABA level of neuronal and glial cells in culture]. 21

A decrease in brain GABA concentration has been implied as the cause of convulsions induced by hyperbaric oxygen (HOP). We therefore examined the influence of sodium valproate, an anticonvulsant and GABA transaminase inhibitor on HOP-induced convulsions in rats. The mean latency of occurrence of the first electrical discharge in the ECoG and the appearance of the first clinical seizure in awake chronically implanted rats was unchanged by administration of sodium valproate prior to HOP exposure. We conclude that either the sodium valproate inhibition of GABA removal is insufficient to compensate for HOP inhibition of its production, or else that GABA concentration changes are not causally related to HOP-induced seizures.
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PMID:Influence of a GABA transaminase inhibitor on central nervous system oxygen toxicity. 35 31

Diazepam-induced GH secretion was tested on 28 male volunteers before and after a 3-day treatment with methysergide, pimozide, or sodium valproate. Serum GH, diazepam, and blood glucose levels were determined. Without prior medication, the mean serum GH level increased 336% 1 h after diazepam administration. Treatment with the serotonin antagonist, methysergide, had no effect on the diazepam-stimulated GH secretion, whereas pimozide, the selective dopamine receptor-blocking agent, reduced the GH response to diazepam by 50% (P less than 0.05). Sodium valproate, a gamma-aminobutyric acid transaminase inhibitor, also inhibited diazepam-induced GH secretion; stimulated GH levels were 51% at 30 min (P less than 0.025), 39% at 60 min (P less than 0.025), and 46% at 90 min (P less than 0.025) relative to the stimulated levels without medication. No difference was found in blood glucose or serum diazepam levels after the drug treatments relative to the values obtained under basal conditions. It is suggested that diazepam-induced GH secretion is at least partly mediated via dopaminergic mechanisms. Serotonin does not seem to be involved. It is further proposed that gamma-aminobutyric acid plays an inhibitory role in GH secretion.
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PMID:The effect of methysergide, pimozide, and sodium valproate on the diazepam-stimulated growth hormone secretion in man. 37 Jan 37

1. The maternal to foetal transfers of S(+)- and R(-)-gamma-vinyl-GABA (VGB) across the human isolated perfused placenta were low and comparable with those of acidic alpha-amino acids. 2. The placental uptake of the active S(+)-isomer from the maternal circulation exceeded that of the R(-)-isomer and this was reflected by a corresponding difference in placental tissue concentrations. 3. During perfusion with recirculation of the foetal medium, the two enantiomers were present at a similar concentration and did not concentrate in foetal perfusate, indicating that the excess amount of S(+)-VGB cleared from the maternal circulation was not accessible to the foetal perfusate. Furthermore, stable concentrations of both isomers in the foetal perfusate suggested a lack of placental metabolism. 4. Possible explanations of these findings include the operation of a stereoselective sodium-dependent-GABA placental uptake system on the maternal side, similar to that observed in neuronal tissue, or stereoselective binding to a placental GABA transaminase.
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PMID:Passage of S(+) and R(-) gamma-vinyl-GABA across the human isolated perfused placenta. 141 75

The effects of adding vigabatrin (GVG) to the antiepileptic regimens of 16 children with refractory epilepsy have been studied. One-half of the regimens included sodium valproate (VPA). Parameters studied were seizure reduction, platelet GABA-T activity, and steady-state plasma concentrations (CSS) of GVG and VPA. Add-on GVG reduced the seizure frequency both in patients receiving VPA (from 42.9 to 4.5 seizures/month, p < 0.01) and in those without VPA (from 60.0 to 31.7 seizures/month, p < 0.05). GVG also reduced GABA-T activity in both groups (from 19.4 to 5.4, p < 0.001 and from 8.3 to 4.5 pmol/min/mg of protein, p < 0.05, respectively). Seizure reduction and GABA-T inhibition were greater in patients taking VPA than in those who were not. In patients receiving VPA, no significant changes were observed in VPA CSS values before and after the addition of GVG. On the other hand, no differences were found in GVG CSS values between patients with and without VPA. It is concluded that the coadministration of GVG to valproate reduces the frequency of seizures in refractory epileptic children and does not affect the steady-state plasma concentrations of either drug. Therefore, their association could be useful in clinical practice.
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PMID:Coadministration of vigabatrin and valproate in children with refractory epilepsy. 147 47

The effect of gamma-aminobutyric acid (GABA) on the human internal anal sphincter was investigated. Cumulative applications of GABA produced concentration-dependent contractions (10(-8)-10(-5) M) of the isolated human sphincter. Pretreatment with bicuculline (GABAA antagonist) turned them to relaxation. Muscimol, a GABAA agonist, induced concentration-dependent contractions (10(-8)-10(-5) M); however, baclofen (GABAB agonist, 10(-8)-10(-5) M) promoted concentration-dependent relaxation of the strips. These results suggested that both excitatory GABAA receptors and inhibitory GABAB receptors exist in the internal anal sphincter. Oral administration of sodium valproate (1600 mg/day), a GABA transaminase inhibitor, enhanced the anal canal resting pressure in 10 normal volunteers. Anal manometry showed a significant elevation in tonus without affecting amplitudes or frequencies. These results indicated that endogenous GABA, which was increased by sodium valproate, produced elevations in the anal canal resting pressure through its specific receptors in the human internal anal sphincter.
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PMID:gamma-Aminobutyric acid enhances the tone of human internal anal sphincter. 165 45

Effects of drugs which enhance or reduce GABAergic neurotransmission upon conflict behavior were evaluated with a modified Vogel procedure which was shown to be insensitive to variations in motivation to drink and to the analgesic effects of morphine. In addition, the effects of these drugs on ambulatory activity and motor execution were quantified. For comparison, the benzodiazepines diazepam and chlordiazepoxide were used. Anticonflict actions of diazepam were obtained with a shock current of 0.25 mA but not with 0.05 or 0.5 mA, whereas the proconflict effect of FG7142 was obtained with 0.05 mA but not with higher currents. Diazepam and chlordiazepoxide had anxiolytic effect in a dose similar to that required to reduce ambulatory activity, but below that needed to affect motor execution. At doses high enough to impair motor execution, anticonflict effects were considerable. The GABA-A receptor agonist THIP and the GABA-B receptor agonist baclofen lacked effect on conflict behavior in moderate doses, which reduced ambulatory activity. In doses which produced motor deficiencies these drugs reduced licking both in the conflict test and when tested without shock administration. The effects of the GABA transaminase inhibitors gamma-acetylene GABA and sodium valproate were similar to those of the receptor agonists. The GABA reuptake inhibitor SKF 100330A produced anticonflict effect in a dose below that needed to reduce ambulatory activity, but lacked effect on conflict behavior in higher doses. The GABA antagonist picrotoxin, and the GABA synthesis inhibitors 4-deoxypyridoxine and isoniazide, reduced licking both in the absence and presence of shock, and affected motor functions in the same doses. Bicuculline, at the doses used, had no behavioral effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GABAergic drugs and conflict behavior in the rat: lack of similarities with the actions of benzodiazepines. 166 Jan 3


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