Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.19 (GABA transaminase)
808 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty sheep were used to study the mechanisms by which the intracerebral administration of pentobarbital and of muscimol induces feeding in ruminants. Injections of 1 mumol calcium induced a weak feeding response at 1 h postinjection compared with control values (108 vs. 63 g, p less than 0.05). Injections of 78 mumol pentobarbital and of 100 nmol muscimol elicited strong feeding responses (p less than 0.01). A preinjection of 1 mumol calcium reduced the response to pentobarbital by about 40% but did not affect the response to muscimol. Administration of 1.1 mmol sodium chloride reduced the effect to pentobarbital by about 60% but only partially decreased the effect to muscimol. Administration of picrotoxin, a GABA antagonist, slightly decreased the feeding response to pentobarbital and to muscimol. Administration of gamma-vinyl GABA, an inhibitor of the enzyme GABA transaminase, did not affect feeding behavior of sheep at any of the doses tested (0-10 mumol). Injections of gamma-vinyl GABA followed by equimolar injections of GABA failed to provoke any feeding response. The data suggest that pentobarbital and muscimol may induce feeding by acting on a similar hypothalamic receptor complex but by different mechanisms. The lack of effect of GABA itself remains unexplained.
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PMID:Comparison between pentobarbital- and muscimol-induced feeding in satiated sheep. 316 84

Previous cytoarchitectural and electron micrographic studies have indicated that the gustatory zone of the nucleus of the solitary tract (NST) may contain local circuit neurons. It is known that neurons of the caudal "visceroceptive" NST contain GABA, glutamic acid decarboxylase (EC 4.1.1.15), and GABA-transaminase (GABA-T; 4-aminobutyrate: 2-oxoglutarate aminotransferase; EC 2.6.1.19). The present study was conducted to determine whether or not neurons in the gustatory zone of the NST of rat contain GABA and the principle degradative enzyme of GABA, GABA-T. Transganglionic transport of horseradish peroxidase (HRP) was used to identify chorda tympani (CT) nerve terminal fields. Immunohistochemical studies were combined with transport experiments to evaluate the organization of GABA immunoreactive neurons in CT terminal fields. Results show that GABA immunoreactive neurons and puncta are located within CT terminal fields. These neurons evince small ovoid morphologies resembling Golgi interneurons, and comprise an average of 18% of total neurons in CT terminal fields. Independent histochemical studies reveal that approximately 82% of GABA immunoreactive neurons within CT terminal fields exhibit GABA-T activity. Retrograde transport of HRP was used in additional studies to evaluate whether or not axons of putative GABAergic neurons project to the second-order central gustatory relay located in the caudal parabrachial nucleus (PBNc), to the caudal NST, or to regions surrounding the rostral or caudal NST. Combined studies indicate that GABA immunoreactive neurons in the gustatory NST do not project axons to the PBNc, to the caudal NST, or to regions adjacent to the rostral or caudal NST.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Organization of GABA and GABA-transaminase containing neurons in the gustatory zone of the nucleus of the solitary tract. 320 50

Acute exposure of adult male albino rats (110-120 g) to higher environmental temperature (40 +/- 1 degrees C) increased body temperature (BT). This increase of BT was also dependent on the duration of exposure. Treatment with muscimol (1 mg/kg, i.p.), a GABA agonist, produced hypothermia at room temperature (28 +/- 1 degree C) and resistance to increase the body temperature when exposed to higher temperature (40 +/- 1 degree C). Administration of bicuculline (1 mg/kg, i.p.), a GABA antagonist, on the other hand, enhanced BT more than that observed in control (normal) rat exposed to higher temperature (40 +/- 1 degree C), although at room temperature bicuculline treatment did not show any effect on BT. Pretreatment with ethanolamine-O-sulfate (EOS) (2 g/kg, s.c.), a GABA transaminase inhibitor, to rats exposed to higher temperature increased BT as in control (normal) rat. Inhibition of central GAD activity with mercaptopropionic acid (MPA) (70 mg/kg, i.p.) produced resistance to increase BT during its period of action when rats were exposed to higher environmental temperature (28 +/- 1 degree C). These results thus suggest that central inhibitory neuron, GABA, plays a regulatory role in thermoregulation.
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PMID:Involvement of GABA in environmental temperature-induced change in body temperature. 323 43

We report here the first purification to homogeneity of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19) (GABA-T) from an invertebrate source (locust) and its initial comparison with that of GABA-T from mammalian brain (sheep). The enzyme from both organisms was found to be a dimer of similar-sized subunits, with a native Mr of approx. 97,000. The pI of GABA-T from the locust was 6.7 and that of the sheep enzyme was 5.5. Michaelis constants for 4-aminobutyric acid (GABA) and 2-oxoglutarate were respectively 0.79 +/- 0.16 mM and 0.27 +/- 0.08 mM for the locust enzyme and 2.2 +/- 0.24 mM and 0.22 +/- 0.11 mM for the sheep enzyme. 5-(Aminomethyl)-3-isoxazolol (muscimol) was a competitive inhibitor of both enzymes, whereas 5-amino-1,3-cyclohexadienylcarboxylic acid (gabaculine) acted as a potent suicide substrate. However, 3-aminopropane-1-sulphonic acid, diaminobutyric acid, 1,2,3,4-tetrahydro-1-methyl-3-pyridinecarboxylic acid (isoguvacine), beta-(aminomethyl)-4-chlorobenzenepropanoic acid (baclofen), bicuculline and picrotoxin did not inhibit either enzyme at concentrations below 100 mM. Polyclonal antisera raised against GABA-T from the sheep failed to cross-react with the enzyme from locust in either an Ouchterlony immunodiffusion plate or a competitive enzyme-linked immunosorbent assay. The purification procedures differed considerably. Ion-exchange chromatography, which was found suitable for the purification of GABA-T from the sheep, was ineffective with locust enzyme, which was finally purified by hydrophobic-interaction chromatography and chromatofocusing.
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PMID:Purification and partial characterization of 4-aminobutyrate:2-oxoglutarate aminotransferase from sheep brain and locust ganglia. 335 98

Hepatic coma was induced in rats chronically treated with CCl4, by means of a single injection of ammonium acetate. The activities of glutamate decarboxylase (GAD) and GABA transaminase (GABA-T), as well as the synaptosomal uptake and release of [3H]GABA, were measured in the following brain areas of the comatose rats: cortex, striatum, hypothalamus, hippocampus, midbrain and cerebellum. Hepatic coma was associated with a general decrease of GAD activity, whereas GABA-T activity was diminished only in the hypothalamus, striatum and midbrain. During hepatic coma, the K+-stimulated [3H]GABA release was notably diminished in the striatum and cerebellum, whereas a significant increase was observed in the hippocampus. [3H]GABA uptake increased in most regions after CCl4 treatment, independently of the presence of coma. The results indicate that GABAergic transmission seems to be decreased in most cerebral regions during hepatic coma.
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PMID:Regional brain GABA metabolism and release during hepatic coma produced in rats chronically treated with carbon tetrachloride. 336 28

Suppression of kindled amygdala seizures in rats followed bilateral infusion of the GABA transaminase inhibitor gamma-vinyl-GABA (GVG) into the endopiriform area of the forebrain. The deep prepiriform cortex of the rat is an important site for both initiation and arrest of generalized seizures induced by systemic convulsants. To determine whether this area also regulates the spread of amygdala seizures, the irreversible GABA-transaminase blocking agent, GVG (vigabatrin) was infused bilaterally in the deep prepiriform area in amygdala-kindled rats. Twenty-four hours after the infusion, kindled seizure threshold was elevated in 12 of 13 rats tested. If homologous areas exist in the primate brain, treatment strategies that take advantage of critical areas for seizure spread by local infusion of inhibitory agents or transplantation of GABA-containing cells may be developed for suppressing intractable seizures in humans.
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PMID:gamma-Vinyl GABA in endopiriform area suppresses kindled amygdala seizures. 339 Nov 46

1. Oral administration of the GABA transaminase inhibitor ethanolamine-O-sulphate (EOS, 5 mg/ml in drinking water) to rats for 14 days suppressed food intake by 24%, but reduced weight gain by over 35%. 2. Thus, feed efficiency (g gain/MJ eaten) was decreased by over 15% in EOS-treated rats, suggesting that there had been an increase in metabolic rate. 3. The thermogenic response (rise in oxygen consumption, VO2) to injection of noradrenaline was enhanced by 50% and the thermogenic activity of brown adipose tissue (BAT, assessed from mitochondrial GDP-binding) was increased by 38% in EOS-treated rats. 4. Injection of baclofen (a GABAB agonist, 0.5 mg/kg s.c.) stimulated VO2 in both groups, with a significantly greater response in EOS treated rats, and this was enhanced by bicuculline (GABAA antagonist, 0.5 g/kg s.c.) in control rats and attenuated by muscimol (GABAA agonist, 0.5 mg/kg s.c.) in control and EOS-treated rats. 5. The data indicate that increasing brain GABA concentrations with EOS results in lower levels of metabolic efficiency and increases in thermogenesis.
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PMID:Chronic inhibition of GABA transaminase results in activation of thermogenesis and brown fat in the rat. 341 1

Biochemical and pharmacological effects of gamma-vinyl GABA (Vigabatrin, GVG), and irreversible enzyme-activated inhibitor of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19; GABA-T), were measured in mice. This anticonvulsant produced a time- and dose-dependent elevation of the GABA, phenylalanine and lysine contents of cortical tissue and simultaneously decreased glutamate, aspartate and alanine levels. In addition, GVG caused a biphasic change in glutamine concentrations (a decline 1-4 hours after administration, followed 20 hours later by an increase). Moreover, we found a new, as yet unidentified amino acid in the brain eluting with the same retention time as alpha-aminoadipic acid from an HPLC cation-exchange column. The level of this novel chemical entity was greatly increased by GVG 20 hours after injection of the drug. At all tested intervals between 1 and 60 hours after injection, GVG was ineffective against maximal electroshock. The GABA-T inhibitor dose-dependently protected mice against isoniazid-induced seizures, simultaneously causing an increase in brain GABA concentrations. However, this apparent correlation applied only until 4 hours after treatment. To better define the anticonvulsant profile of GVG, groups of mice were treated, 1, 2, 4, and 24 hours prior to challenge with convulsant doses of strychnine, pentetrazole (PTZ), and picrotoxin, and brain amino acid levels, including brain concentrations of GVG, were measured. In all instances, the time dependency of the anticonvulsant effects of GVG and of increases in brain GABA levels differed. Amino acid concentrations in animals treated only with GVG were similar to those in animals given GVG and a chemical convulsant. GVG showed no selectivity for seizures produced by impairment of GABA-ergic neurotransmission. Although GVG is an effective GABA-T inhibitor, it apparently affects several other pyridoxal-phosphate-dependent cerebral enzymes and/or interacts with other neurotransmitter systems as well.
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PMID:Gamma-vinyl GABA: comparison of neurochemical and anticonvulsant effects in mice. 341 34

3-Nitro-1-propanamine is a close structural analog of the neuro-transmitter GABA. The nitro compound is a good substrate for the GABA aminotransferase from porcine brain. However, it inactivates the GABA aminotransferase from GABA-grown Pseudomonas fluorescens in a slowly reversible reaction. Both enzymes are inactivated by the homolog 4-nitro-1-butanamine.
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PMID:Inactivation of GABA aminotransferase by 3-nitro-1-propanamine. 350 12

Different methods for measuring GABA turnover in rat brain were compared. One method was based on the irreversible inhibition of GABA transaminase (EC 2.6.1.19) by microinjection of gamma-vinyl-GABA into neostriatum of rat. The accumulation of GABA was almost linear for 4 hr. The GABA turnover in control animals was estimated to be 25.8 +/- 1.1 nmole/mg protein/hr. Another method was based on the post mortal increase in GABA level in an 8 min interval after decapitation. This method gave a GABA turnover of 54.3 +/- 4.8 nmole/mg protein/hr in neostriatum. The methods were compared with respect to their ability to detect the effect of high doses of diazepam and morphine on the turnover rate of GABA. The GABA transaminase inhibition method resulted in a 27% and a 17% decrease in GABA turnover for diazepam and morphine respectively. The post mortem method did not detect any change in GABA turnover after administration of these drugs. Hypoglycemia leads to a decrease in GABA turnover of 17% with the GABA transaminase inhibition method and a 43% decrease in GABA turnover with the post mortem method. The advantages and limitations of the methods for estimating GABA turnover changes during drug exposure is discussed, and are compared with results from a third method based on steady state kinetics extracted from the literature.
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PMID:Comparison of results obtained with different methods for estimating GABA turnover in rat neostriatum. 355 8


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