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)

Benzodiazepine (BZD) anxiolytics, through their activation of the BZD-GABA receptor complex, display robust anxiolytic-like effects following systemic administration in both conditioned and non-conditioned behavioral procedures. The present results show that the GABAA agonists muscimol (0.5-1.0 mg/kg), THIP (2.5-10.0 mg/kg), and isoguvacine (25.0 mg/kg) as well as the GABA transaminase (GABA-T) inhibitor AOAA (aminooxyacetic acid; 5.0-20.0 mg/kg) following intraperitoneal administration exert anxiolytic-like activity of similar magnitude to that of diazepam in two non-conditioned procedures, namely the social interaction and the elevated plus maze tests. We have also extended our original findings that the anti-epileptic drug sodium valproate exerts an anxiolytic-like effect in the Geller conflict paradigm, to show this agent's robust activity in the social interaction and elevated plus maze tests following systemic administration (100-400 mg/kg). These results show that GABAergic agents that facilitate GABA transmission are effective following systemic administration in non-conditioned anxiety procedures and may indicate potential therapeutic efficacy in certain anxiety states.
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PMID:GABAmimetic agents display anxiolytic-like effects in the social interaction and elevated plus maze procedures. 168 57

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 effects of enhanced central nervous system GABA levels on sexual behavior and copulatory pelvic thrusting were evaluated in male New Zealand white rabbits. The GABA transaminase inhibitors sodium valproate and gamma-acetylen GABA (GAG), in doses of 100 and 200 mg/kg and 50 and 100 mg/kg, respectively, were intraperitoneally administered and sexual behavior recorded at several intervals after drug administration. At the same time, copulatory thrusting was registered using a polygraphic technique. Tests for gross motor functions were also performed. None of the drugs had any effect in these latter tests. Sodium valproate, in a dose of 100 mg/kg, had a slight inhibitory effect on sexual behavior at 280 min postinjection. A dose of 200 mg/kg inhibited sexual activity already 15 min postinjection, and the effect lasted for at least 280 min. GAG, 100 mg/k, inhibited mounting behavior at 8 h postinjection, and ejaculation was reduced from 2 to at least 8 h postinjection. Copulatory thrusting patterns were not affected by the drug treatments. These data suggest that increased GABAergic activity reduces sexual arousal in the rabbit. GABA does not seem to be critically involved in the regulation of the motor patterns underlying pelvic thrusting. There are important quantitative and qualitative differences between rats and rabbits with regard to the actions of GABA transaminase inhibitors upon sexual functions.
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PMID:Sexual behavior and copulatory thrusting patterns in male rabbits treated with GABA transaminase inhibitors. 201 84

It has previously been found that the GABA transaminase inhibitors gamma-acetylen GABA (GAG) and sodium valproate reduced intromission behavior in male rats without affecting mounting behavior. These effects were obtained, however, only in doses that also impaired motor execution. The purpose of the present study was to establish whether copulatory thrusting patterns were affected by these GABA transaminase inhibitors. Sodium valproate, 200 mg/kg, reduced the number of intromissions and the intromission rate without affecting mounting behavior. GAG, 100 mg/kg, had similar effects on sexual behavior. The only effect obtained on copulatory thrusting patterns was a small reduction in mount and intromission thrust frequency after GAG 100 mg/kg. It is unlikely that this effect is responsible for the inhibitory actions of GAG on sexual behavior, especially since sodium valproate did not modify copulatory thrusting patterns, but inhibited sexual behavior in a manner similar to that of GAG.
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PMID:Copulatory thrusting pattern in the male rat after acute treatment with GABA transaminase inhibitors. 215 60

The tetrazolium salt procedure of van Gelder (1965) for the demonstration of GABA transaminase (GABAT; the most important GABA degrading enzyme) was adapted for microphotometric measurements of GABAT activities in brain sections using the hippocampus of rats as selected brain region. The final incubation medium consisted of 50 mM GABA, 5 mM alpha-ketoglutarate, 7 mM NAD, 10 mM sodium azide, 6 mM nitroblue tetrazolium chloride, 20 mM malonate and 15% polyvinyl alcohol in 0.05 M Hepes buffer; the final pH was 8.0. There was a linear relationship between GABAT activity and section thickness up to 14 microns and between GABAT activity and reaction time at least up to 20 min (kinetic and end-point measurements). Phenazine methosulfate as an exogenous electron carrier and pyridoxal-5-phosphate as coenzyme of GABAT did not enhance the demonstrable GABAT activities, whereas sodium azide as a blocker of the respiratory chain resulted in an increase of demonstrable enzyme activities. A coreaction of succinate dehydrogenase was excluded by the use of malonate (competitive inhibitor). Using the incubation medium described GABAT activities were demonstrated via the endogenous enzymes succinic semialdehyde dehydrogenase and NADH tetrazolium reductase which were shown to be not rate limiting and seems to be similarly localized as GABAT.
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PMID:Microphotometric determination of enzymes in brain sections. II. GABA transaminase. 233 51

The binding of 4-amino-n-[2,3-3H]butyric acid (GABA) to receptor sites in the supraoesophageal ganglia of the locust Schistocerca gregaria is reported. Binding is saturable with a Kd of 30 nM and a Bmax of 150 fmol/mg protein. Binding is sodium-independent with a pH optimum of 6.8 and the pharmacological properties of the site suggest a receptor rather than an uptake or transport protein. The assay is being utilised in a comparative study of the binding sites of the GABA receptor and the enzyme 4-aminobutyrate: 2-oxoglutarate amino-transferase (EC 2.6.1.19, GABA-T). GABA binds to at least 4 proteins in the nervous system of vertebrates: the GABAA and GABAB receptors, GABA-T the enzyme involved in the GABA shunt, and the GABA transport system. In the invertebrates the status of these GABA-binding proteins is less well established. There are reports of a GABA receptor complex resembling the GABAA receptor; GABA-T activity has been reported and we have recently purified the enzyme from locust ganglia; it is assumed that GABA uptake systems are present in invertebrates. Proteins with different functions which specifically bind the same ligand are interesting from an evolutionary point of view. Are they distinct gene products or is the sub-unit of the receptor which binds GABA an enzyme which has lost the ability to bind pyroxidal phosphate? Do either receptor or enzyme differ significantly from their mammalian counterparts?
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PMID:GABA binding to receptor sites in locust supraoesophageal ganglia. 282 55

In an attempt to identify potential anticonvulsant compounds, 18 structural analogues of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) were tested for their ability to inhibit GABA receptor binding, sodium-dependent GABA binding and GABA aminotransferase activity in synaptic membranes from mouse brain. Nine inhibitors of receptor binding were found. The most potent was N-(thiocarbamoyl)glycine (Ki = 18 microM). However, this compound had no real effect on Na+ -dependent GABA binding nor on the activity of GABA aminotransferase. In addition, it was unable to enhance the binding of [3H]flunitrazepam as GABA agonists usually do. This could indicate that this inhibitor is, rather, a GABA receptor antagonist. Even though no particularly potent inhibitors of any of the GABA recognition sites were found, this technique nevertheless demonstrates how simple in vitro assays can be used to find drugs exhibiting potential GABA-mimetic activity.
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PMID:Identification of potential GABA-mimetics by their actions on brain GABA recognition sites. 298 86

Anticonvulsant sodium valproate, an inhibitor of GABA transaminase, which induces GABA accumulation in the brain, has been shown to possess a potent antiarrhythmic effect. In acute ischemia and reperfusion in conscious rats with closed chest, it decreased fourfold total duration of arrhythmias, while in nonanesthetized animals with open chest, it substantially limited the heart electrical fibrillation threshold and reduced fourfold total duration of arrhythmias. In both experimental models, sodium valproate decreased threefold the rate of ischemia-induced heart fibrillations. Clinicophysiological evaluation of the effect of sodium valproate on arrhythmias in coronary patients appears warranted.
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PMID:[Prevention of arrhythmias and cardiac fibrillation in acute ischemia and reperfusion by using a factor causing GABA accumulation in the brain]. 311 16

The GABA transaminase inhibitors gamma-acetylen GABA (GAG) and sodium valproate were administered intraperitoneally and their effects on locomotor activity, motor execution and sexual behavior were analyzed. It was found that sodium valproate, administered 15 min before observation, reduced locomotor activity only at a dose of 200 mg/kg. Doses of 100 and 400 mg/kg had no effect. Motor execution was impaired in a dose-dependent way, the lowest effective dose being 200 mg/kg. Sexual behavior was also dose-dependently reduced. Sodium valproate, administered 60 min before observation, inhibited all behaviors. The lowest effective dose was 200 mg/kg for locomotor activity and 400 mg/kg for motor execution and sexual behavior. GAG also inhibited all behavior, in doses ranging from 25 mg/kg (locomotor activity) to 100 mg/kg (motor execution and sexual behavior). The data showed that there is no relation between effects on locomotor activity and the effects on sexual behavior, whereas sexual behavior is inhibited whenever motor execution is impaired. Moreover, there is no correlation between effects on locomotor activity and motor execution. It is suggested that GABA transaminase inhibitors effect sexual behavior only indirectly, via an impairment of motor execution. Therefore it is doubtful whether GABAergic mechanisms play any role in the normal regulation of sexual behavior.
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PMID:Differential effects of GABA transaminase inhibitors on sexual behavior, locomotor activity, and motor execution in the male rat. 311 62

Serum concentrations of gamma-aminobutyric acid (GABA) are increased in liver failure, possibly because of decreased hepatic GABA catabolism. To study in detail the role of the liver in GABA metabolism, uptake and catabolism of GABA by isolated perfused liver from normal rats and rats with galactosamine- or carbon tetrachloride-induced liver failure were measured. Hepatic GABA uptake was almost complete at GABA concentrations of up to 10 microM and approached saturation at a concentration of 50 microM. The apparent affinity of hepatic GABA uptake was 38 microM and the apparent maximal velocity was 158 nmol/g.min. Hepatic GABA uptake was sodium-dependent. gamma-Aminobutyric acid taken up by the liver was rapidly catabolized as measured by 14CO2 formation from [U-14C]GABA. Aminooxyacetic acid, a GABA transaminase inhibitor, completely and irreversibly inhibited hepatic GABA catabolism and thereby also inhibited hepatic GABA uptake. Although uptake of GABA by livers of carbon tetrachloride- or galactosamine-treated rats was decreased (apparent maximal velocity, 103 and 98 nmol/g.min, respectively), at physiologic GABA concentrations in the perfusate GABA uptake and catabolism was not different from that of untreated controls. The observed impairment of hepatic GABA uptake or catabolism by the diseased liver would be expected to contribute to increased GABA levels in peripheral blood plasma in liver failure. However, the magnitude of the observed impairment would be insufficient to account for a 10-fold increase in such levels.
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PMID:Uptake and catabolism of gamma-aminobutyric acid by the isolated perfused rat liver. 339 67


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