Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.19 (GABA transaminase)
 808 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seizure susceptibility and GABA metabolism were altered in the substantia nigra [SN] of adult male Sprague Dawley rats when these animals were acclimating to an altered plasma osmolality. Changes in GABA metabolism were measured in vivo in SN of the freely moving rat. Suitable precautions were taken to avoid any post-mortem flux of glutamate to GABA and to correct for the underestimation of GABA build up in SN due to the finite diffusion rate of gamma-vinyl GABA [GVG] after stereotaxic injection of small amounts into one side of the brain. Control experiments provided evidence that changes in osmolality, within a normal physiological range, did not affect significantly gamma-aminobutyric acid transaminase [GABA-T]. Also kindling via the medial septum [MS], in the absence of electrical stimulation did not alter GABA metabolism in SN, thus providing a stable baseline for studies of osmotic effects. Hyperosmolality was associated with a rise in seizure thresholds, with a marked reduction of the rate of GABA synthesis in SN, and with a substantial increase in turnover time of the GABA pool. Hypoosmolality, of a degree known to be associated with mild cerebral edema and swelling localized to astrocytes, markedly reduced seizure threshold, and reduced GABA pool size in SN, but did not alter the rate of GABA synthesis significantly. These results demonstrate by new and independent means the relationship between GABA metabolism in the SN and seizure susceptibility in vivo.
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PMID:Alterations of GABA metabolism and seizure susceptibility in the substantia nigra of the kindled rat acclimating to changes in osmotic state. 178 28

Synaptosomes isolated from mouse brain were incubated with [14C]glutamate and [3H]gamma-amino-butyric acid ([3H]GABA), and then [14C]GABA (newly synthesized GABA) and [3H]GABA (newly captured GABA) in the synaptosomes were analysed. (1) the [3H]GABA was rapidly degraded in the synaptosomes, (2) when the synaptosomes were treated with gabaculine (a potent inhibitor of GABA aminotransferase), the degradation of [3H]GABA was strongly inhibited, (3) the gabaculine treatment brought about a significant increase in Ca2(+)-independent release of [3H]GABA with no effect on Ca2(+)-dependent release, (4) no effects of gabaculine on degradation and release of [14C]GABA were observed. The results indicate that there are at least two pools of GABA in synaptosomes and support the possibilities that GABA taken up into a pool which is under the influence of GABA aminotransferase is released Ca2(+)-independently and that GABA synthesized in another pool which is not under the influence of GABA aminotransferase is released Ca2(+)-dependently.
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PMID:Effect of gabaculine on metabolism and release of gamma-aminobutyric acid in synaptosomes. 197 70

The effects of dopamine D1 and D2 receptor agonists and antagonists on the rate of GABA synthesis in four regions of mouse brain (corpus striatum, cerebellum, cortex and hippocampus) were examined after irreversible inhibition of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19; GABA-T) by gabaculine. The dopamine D2 receptor agonists PPHT, LY 171555 and RU 24213 exerted a dose-related inhibitory effect on GABA synthesis in these four regions. The decreases in the rate of GABA formation were prevented by the dopamine D2 receptor antagonist S(-)-sulpiride. The dopamine D1 receptor agonists SKF 77434 and SKF 38393 augmented gabaculine-induced GABA accumulation in the corpus striatum only, and this effect was blocked by the dopamine D1 receptor antagonist SCH 23390. However, SKF 81297 and SKF 82958, two other dopamine D1 receptor agonists, did not affect or only marginally altered the rate of GABA synthesis. Stimulation of D2 receptors thus induces a decrease in the rate of GABA formation in the four brain areas examined, whereas stimulation of D1 receptors either increases GABA synthesis in the corpus striatum or does not alter it. This effect appears to be independent of the degree of receptor occupancy.
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PMID:Effects of selective dopamine D1 and D2 receptor agonists on the rate of GABA synthesis in mouse brain. 198 57

The presence of GABAergic innervation in cerebral arteries of several species was investigated by an immunohistochemical method using antibodies against glutamic acid decarboxylase (GAD) and GABA transaminase (GABA-T). Both GAD and GABA-T immunoreactivities were found to be associated with large bundles and single fibers in the adventitial layer of arteries examined. The density and distribution pattern of both GAD- and GABA-T-immunoreactive fibers were found to be comparable at most regions examined. Both fibers were found to be most dense in the anterior cerebral artery and its adjacent part of the circle of Willis. Several peripheral arteries were found to receive very sparse or no GAD- and GABA-T-immunoreactive fibers. Superior cervical ganglionectomy did not appreciably affect the distribution of both fibers. Cold-storage denervation, however, resulted in a drastic decrease in both fibers. At ultrastructural levels, both GAD- and GABA-T-immunoreactive nerve profiles were found to be very close to the smooth muscle cells. These results demonstrate the presence of a potentially functional GABAergic innervation in cerebral circulation. On few occasions, GAD immunoreactivities were also found in some endothelial cells, suggesting that a nonneuronal GABA system may also be present in cerebral arteries.
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PMID:GABAergic innervation in cerebral blood vessels: an immunohistochemical demonstration of L-glutamic acid decarboxylase and GABA transaminase. 198 97

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

Low-frequency vibration, irrespective of its duration (20 Hz, A = 0.4 mm), is shown to increase GABA level, glutamatedecarboxylase enzyme activity (EC 4.1.1.15) in the large hemispheres, cerebellum, brain stem of adult male rats (12 months). Meanwhile GABA aminotransferase activity (EC 2.6.1.19) remains, mainly, unchanged. The observed shifts are more clear under 30 min vibration than under 7h and 30 day effects. Glutaminic and aspartic acids content increases under 30 min and decreases under 7h and 30 day vibration in the given brain structures.
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PMID:[The effect of low-frequency vibration on GABA metabolism in brain structures]. 205 25

Morphine produced a hypothermic effect in restrained rats which was antagonized by naloxone. This effect was completely inhibited by gamma-acetylenic-GABA, an inhibitor of GABA transaminase and by baclofen, a specific GABAB agonist. Pretreatment with diazepam, an agonist of the benzodiazepine receptor, partially inhibited morphine-induced hypothermia. Flumazenil, a benzodiazepine receptor blocker, potentiated the action of morphine on body temperature. A role of brain GABA in the thermoregulatory effects of morphine is proposed on the basis of these results.
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PMID:GABAergic mechanisms in morphine-induced hypothermia. 207 23

The ventral hippocampi of male, Fischer-344 rats were implanted with microdialysis probes and the effects of systemically administered kainic acid (KA) (8 mg/kg, s.c.) on the in vivo release of amino acids were measured for four hours after administration. In order to measure GABA release in vivo, gamma-vinyl-GABA (GVG), an irreversible inhibitor of GABA transaminase, was injected intrahippocampally prior to perfusion. GVG pretreatment resulted in measurable levels of GABA in the perfusate without significant effects on the release of aspartate, glutamate, glutamine, glycine or taurine. Following GVG pretreatment systemic administration of KA produced a time-dependent increase in GABA, as well as all other amino acids except glutamine, which was initially decreased. These results show for the first time that systemically administered KA increases extracellular GABA levels, an effect previously reported only in vitro. These data suggest that prior to destruction of GABA-containing interneurons in the hippocampus, there is an increased activity of those GABA interneurons reflected as an increase in extracellular GABA levels.
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PMID:Systemic administration of kainic acid increases GABA levels in perfusate from the hippocampus of rats in vivo. 208 85

Gabaculine, 5-amino-1,3-cyclohexadienylcarboxylate, is an analogue of GABA and a potent irreversible inhibitor of GABA aminotransferase. However, D-3-aminoisobutyrate-pyruvate aminotransferase for which GABA was neither a substrate nor an inhibitor was also inactivated by gabaculine. The Ki for D-3-aminoisobutyrate-pyruvate aminotransferase was 8.3 x 10(-6) M, and the Kcat for its turnover was 0.31 min-1 at 25 degrees C. beta-Alanine protected the enzyme from inactivation by gabaculine, but GABA did so to much a lesser extent.
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PMID:Irreversible inhibition of D-3-aminoisobutyrate-pyruvate aminotransferase by gabaculine. 212 4

Pretreatment with 5-hydroxytryptophan (5-HTP), a precursor of 5-HT, antagonised while pretreatment with p-chlorophenylalanine (PCPA), a 5-HT depletor, potentiated the myoclonus induced by picrotoxin, a GABA antagonist. Pretreatment with aminooxyacetic acid (AOAA), a GABA transaminase inhibitor, antagonised picrotoxin-induced myoclonus. The combined effect of the least protective doses of AOAA and 5-HTP was greater than the sum of their individual inhibitory effects on picrotoxin-induced myoclonus. Further, AOAA failed to inhibit picrotoxin-induced myoclonus in PCPA pretreated rats. These findings suggest that the central 5-HT-ergic system exerts a facilitatory influence on the GABA-ergic system and thus it is involved in the antimyoclonic action of GABA.
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PMID:A functional interaction between GABA and 5-HT in inhibiting picrotoxin-induced myoclonus in rats. 214 69


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