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)

A study was made of the effect of X-rays (4,5 Gy) and pyridoxal phosphate (3 mg/kg, v/v) on the activity of pyridoxal enzymes of GABA metabolism (e.g. glutamate decarboxylase, E.C. 4.1.1.15) and aminobutyrate aminotransferase (GABA-T, E.C. 2.6.1.19), as well as on GABA and glutamate content of the hemisphere cortex, brain stem and cerebellum of rabbits 6 and 10 days following irradiation and injection of a coenzyme. The height of the radiation sickness in rabbits was characterized by the manifest changes in glutamate decarboxylase and GABA-T activity, as well as in GABA and glutamate content of various brain parts differing in the structural and functional functions. The administration of pyridoxal phosphate produced pronounced activation of glutamate decarboxylase, particularly 6 days after irradiation and administration of the co-enzyme, and, to a lesser extent, influenced GABA-T function. Pyridoxal phosphate favored maintaining the GABA level above the control level in the hemisphere cortex and brain stem 6 and 10 days after exposure. The injection of pyridoxal phosphate did not normalize the glutamate content of the brain parts 6 days after exposure, but favored the normalization of GABA-T activity on day 10.
 ...
PMID:[Effect of pyridoxal phosphate on gamma-aminobutyric acid metabolism in different sections of the brain in irradiated animals]. 167 11

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.
 ...
PMID:GABAmimetic agents display anxiolytic-like effects in the social interaction and elevated plus maze procedures. 168 57

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.
 ...
PMID:Alterations of GABA metabolism and seizure susceptibility in the substantia nigra of the kindled rat acclimating to changes in osmotic state. 178 28

(4S)-4-Amino-5,6-heptadienoic acid [S)-gamma-allenyl-GABA; MDL 72483) is a potent inactivator of brain GABA-T in mice; (ED50 (i.p.) = 60 mg.kg-1; ED50 (oral) = 70 mg.kg-1). Its anticonvulsant effects against 3-mercaptopropionic acid (MPA)-induced seizures in mice is related to the elevation of whole brain GABA concentrations: The mentioned doses of MDL 72483 which cause a decrease of GABA-T activity by 50%, produce within 5 h after dosing an increase of GABA concentration by about 3 mumol.g-1, and protect 50% of the mice against seizures in this model of presynaptic GABA deficit. When given orally MDL 72483 is about five times more potent than vigabatrin [4R/S)-4-amino-5-hexenoic acid) a known antiepileptic GABA-T inhibitor. Complete protection was achieved with a dose of 150 mg.kg-1. Similar to vigabatrin, MDL 72483 does not protect significantly against metrazol-induced convulsions. However, at a dose of 300 mg.kg-1, the time elapsing between metrazol administration and onset of convulsions was prolonged by a factor of 3.4. Oral administration of MDL 72483 for up to 19 days at a daily dose of 91-96 mg.kg-1 did not produce any obvious behavioral changes in mice, nor was the ED50 of the drug in MPA-seizure tests significantly altered by the pretreatment. These observations indicate that MDL 72483 is a promising drug for the treatment of certain epilepsies.
 ...
PMID:(4S)-4-amino-5,6-heptadienoic acid (MDL 72483): a potent anticonvulsant GABA-T inhibitor. 178 30

Overall glutamate decarboxylase (GDCase) activity in the initial mitochondrial fraction of the limbic structure is found to be regionally different it increases from the moment of birth up to 1 year, the midbrain reticular formation (RF), where the enzyme activity in the mitochondrial decreases in pups aged 3 month and reincreases in 1 year old dogs being the exception. Overall GABA-transaminase (GABA-T-ase) activity reaches the "adult" level and is the highest: in the hypothalamic and hippocampal mitochondria on the 1st postnatal day; in the limbic cortex (l1 and l2 fields), amygdala and midbrain RF--on the 12-16th postnatal days. During the period from 12-16 postnatal days up to the age of 1 year GABA-T-ase activity in the dog limbic system decreases reliably.
 ...
PMID:[Glutamate decarboxylase and GABA transaminase activity in the mitochondrial fraction of the dog brain limbic system during postnatal development]. 192 85

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.
 ...
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.
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:[The effect of low-frequency vibration on GABA metabolism in brain structures]. 205 25


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>