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)

The effects of DL-penicillamine (DL-PeA), hydrazine and toxopyrimidine (TXP, 2-methyl-6-amino-5-hydroxymethylpyrimidine) on gamma-aminobutyric acid (GABA) metabolism in mouse brain were studied. All these compounds inhibited the activity of glutamate decarboxylase [EC 4.1.1.15] (GAD) and slightly inhibited that of 4-aminobutyrate: 2-oxoglutarate aminotransferase [EC 2.6.1.19] (GABA-T). In contrast, very different effects were observed on GABA levels; hydrazine caused a marked increase, DL-PeA had no effect, and TXP caused a slight decrease in the content of the amino acid. These results could be described by an equation which related the excitable state to changes in the flux of the GABA bypass. Since the values obtained from the equation clearly reflect the seizure activity, it is suggested that the decreased GABA flux might be a cause of convulsions induced by these drugs.
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PMID:A correlation between changes in gamma-aminobutyric acid metabolism and seizures induced by antivitamin B6. 100 83

The regional distribution of 9 amino acids, including glutamate and GABA and their metabolising enzymes, has been determined in 5 regions of the frog CNS. Glycine was relatively concentrated in the spinal cord whereas the highest concentration of each of the other amino acids was found in the midbrain. There was a good correlation between the activity of l-glutamate-1-carboxylase (GAD) and the level of GABA in all regions examined and both were concentrated in the midbrain. There was little regional variation in the distribution of 4-aminobutyrate-2-oxoglutarate transaminase (GABA-T).
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PMID:Glutamic acid, GABA and their metabolising enzymes in the frog central nervous system. 107 86

A structural similarity of several monobactams (2-4), 3-aminonocardicinic acid (6), 6-aminopenicillanic acid (7), 7-aminocephalosporanic acid (8), and 7-aminodesacetoxycephalosporanic acids (9, 10) to gamma-aminobutyric acid (GABA) and to known inhibitors and substrates of GABA aminotransferase is described. Because of this, the above-mentioned compounds were tested as competitive inhibitors and as inactivators of pig brain GABA aminotransferase. All of the compounds were competitive inhibitors of GABA aminotransferase. On the basis of the inhibitory potency of these conformationally-rigid GABA analogues it is hypothesized that GABA is bound at the active site with its amino and carboxylate groups in a syn orientation. None of the compounds inactivates GABA aminotransferase. These beta-lactam analogues represent the first examples of a new class of inhibitors of GABA aminotransferase.
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PMID:Beta-lactams: a new class of conformationally-rigid inhibitors of gamma-aminobutyric acid aminotransferase. 128 28

The formation and catabolism of aldehydes were compared in the hemispheres and brain stem of rats preferring ethanol (EP) or water (WP) and of those which were high tolerant (HT) and low tolerant to the hypnotic effect of ethanol. It was shown that aldehyde dehydrogenase was more active in the brain stem of HT-EP rats than that of HT-WR or LT-EP animals, whereas GABA aminotransferase is most active in the hemispheres and brain stem of LT-EP rats. The total activity of succinic semialdehyde reductase was equal in all the groups studied; however kinetic analysis suggest that the enzyme has a higher affinity for the substrate and coenzyme in the brain stem of HT-EP rats. Ethanol administered to HT-EP animals suppressed aldehyde dehydrogenase in the brain stem, unchanged GABA aminotransferase and activates succinic semialdehyde reductase in the two brain structures.
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PMID:[The activities of aldehyde dehydrogenase, GABA-aminotransferase and succinic semialdehyde reductase in the brain of rats with different preferences and tolerances for ethanol]. 130 80

The in vivo effects of GABA-ergic drugs on the activity of serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), two enzymes involved in melatonin biosynthesis, were investigated in light-exposed chicken retina. The ip administration of muscimol and baclofen (direct agonists of GABA-A and GABA-B receptors, respectively), aminooxyacetic acid (an inhibitor of GABA transaminase), and nipecotic acid (an inhibitor of GABA reuptake), significantly increased the retinal NAT activity by 50-100%. Similar rises in NAT activity were observed following intraocular treatment of ether-anesthetized chickens with muscimol, baclofen and GABA. In contrast to NAT, there was no effect of the tested drugs on the retinal HIOMT activity. Aminophylline (a phosphodiesterase inhibitor) markedly elevated the retinal NAT activity, and a combined treatment with the GABA-ergic drugs and aminophylline resulted in additive effects. The actions of both muscimol and baclofen were antagonized by picrotoxin and bicuculline (two GABA-A receptor blockers), whereas the effect of baclofen was not changed by a selective GABA-B receptor blocker, CGP 35,348. Melatonin given ip significantly raised NAT activity, and its combination with muscimol further stimulated the enzyme. Picrotoxin and bicuculline given to chickens during the dark phase of 12 h light--12 h dark illumination cycle significantly suppressed the nocturnal NAT activity in retina. Neither GABA nor muscimol and baclofen significantly affected basal and forskolin (1 microM)-stimulated adenylate cyclase activity in vitro in light-exposed chicken retina. It is concluded that a GABA signal (acting through type A of GABA receptors) plays an important role in a complex mechanism regulating the rhythmic melatonin biosynthesis in vertebrate retina.
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PMID:The role of GABA-ergic signal in the regulation of melatonin biosynthesis in vertebrate retina. 130 60

Because of its abundance in the brain, its ability to produce hyperpolarizing inhibition of almost all neurons, its association with benzodiazepines, and the discovery that many convulsants inhibited its synthesis, gamma-aminobutyric acid (GABA) has often appeared to be the key to epilepsy. Many assumed that "primary" or "genetic" epilepsy must be a disorder of GABA synapses and that GABA agonists would be universal anticonvulsants if permeability and drug metabolism were controlled. The GABA synthetic gene was a logical "candidate gene" for epilepsy. However, the GABA-deficiency theory of epilepsy is less convincing today. GABA agonists were found to intensify seizures in some rodent and human cases. Absence and other generalized seizures in humans often worsened when treated with GABA transaminase inhibitors such as gamma-vinyl-GABA. Surprisingly, the GABA transaminase inhibitors appear to be more useful in partial than in generalized epilepsies. Neuronal GABA uptake blockers are proconvulsant. GABA agonists aggravate seizures in several mutants, ranging from the photosensitive baboon to the genetically epilepsy-prone rat. How can this be understood? Muscimol injections into the pedunculopontine nucleus increase seizures due to systematically administered convulsants, while the receptor blocker bicuculline suppresses seizures after injection into several brain regions, including the striatum. The result of inhibiting inhibitory circuits is excitation. Studies with GABA uptake blockers and the GABAB agonist baclofen are presented in which their combined administration provoked seizures in rats. Baclofen was shown also to increase the incidence of seizures evoked by pentylenetetrazole without increasing seizures due to local injections of excitatory amino acids. Baclofen antagonized the myoclonic effect of 5-hydroxytryptophan in rats with serotonin lesions. Baclofen augments some seizures and inhibits others. Selective inhibition of a particular tract, whether GABAergic or not, may have convulsant or anticonvulsant effects, depending on its connections and the state of the organism. GABAA receptor stimulation is usually but not always anticonvulsant. GABAB receptor stimulation may facilitate absence seizures and related primary generalized seizures. GABAB receptors may be abnormal in some forms of nonfocal epilepsy seen in childhood. It is likely that mutations of GABA transporter and GABAA receptor genes will be found in humans but they will probably not be patients with "pure epilepsy."
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PMID:GABA and epilepsy: their complex relationship and the evolution of our understanding. 131 57

The relationship between GABA dynamics and LH release was studied on day 2 after subcutaneous estrogen implant in short-term ovariectomized rats. GABA accumulation, used as an index of GABA turnover, was determined in the medial preoptic nucleus (MPN), medial (MS) and lateral (LS) septal nuclei, median eminence-mediobasal hypothalamus (MBH) and locus ceruleus (LC). Measurements of GABA were performed at two different times of day (11.00 and 15.00 h), 3 h after intraperitoneal administration of gamma-vinyl-GABA (GVG), an irreversible inhibitor of GABA transaminase. Either morning or afternoon ovariectomized rats (OVX) showed a significant increase in GABA accumulation after GVG treatment in all the areas studied. Estrogen-treated OVX rats showed in the morning a lower GABA accumulation in the MPN, MBH and LC, and GABA levels remained unchanged in the LS and MS. In the afternoon, the MPN and LS showed a lower rate of GABA accumulation whereas in the MBH and LC the GABA increase was not observed. In contrast the MS showed a rate of GABA accumulation similar as in the OVX rats. Local administration in the MPN of 20 micrograms GVG, or GABA-A receptor stimulation by muscimol (50 ng), prior to the increase in plasma LH levels, prevented the occurrence of the estradiol-induced LH surge. The effect of muscimol was reversed by bicuculline (30 ng), a GABA-A receptor antagonist. Bicuculline in low doses lacked effect by itself. In conclusion, these results strongly suggest that a decreased GABAergic activity in MPN, MBH and LC precedes the estradiol-evoked LH surges in ovariectomized rats. Moreover, that in septal nuclei, a low GABAergic activity takes place well before the occurrence of plasma LH increase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Restraining action of GABA on estradiol-induced LH surge in the rat: GABA activity in brain nuclei and effects of GABA mimetics in the medial preoptic nucleus. 131 4

To implicate gamma-aminobutyric acid (GABA) as an afferent neurotransmitter (AN), the localization of GABA synthesizing and degradation enzymes; L-glutamate decarboxylase (GAD) and GABA transaminase (GABA-T) was investigated by light and electron microscopy immunocytochemistry in guinea pig vestibular cristae and ganglion cells (GC). GAD-like immunoreactivity was exclusively confined to the sensory hair cell (HC) cytoplasm, suggesting that GAD synthesizes GABA in the HC. GABA-T like immunoreactivity was found within HC, nerve calyces, nerve fibers, and GC, suggesting its participation in terminating transmitter action. These results demonstrate the existence of a GABAergic system in the guinea pig vestibule and strongly support GABA as a vestibular AN.
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PMID:Immunocytochemical evidence for an afferent GABAergic neurotransmission in the guinea pig vestibular system. 132 17

Vigabatrin is a specific gamma-aminobutyric acid transaminase inhibitor. The clinical use of this drug in the treatment of epilepsy has been sporadically linked to the development of psychosis. Using 123I-IBZM, a specific dopamine D2 receptor ligand and single photon emission tomography (SPET), one month of treatment with vigabatrin was associated with a decrease in specific binding of 123I-IBZM to D2 receptors in the left hemisphere basal ganglia. This change may provide one explanation for the development of psychosis in vulnerable patients.
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PMID:Effect of vigabatrin on striatal dopamine receptors: evidence in humans for interactions of GABA and dopamine systems. 132 38

In mice, tonic convulsive seizure induced by intravenous administration of caffeine (adenosine A1, A2 receptors antagonist) was significantly potentiated by any one of L-PIA (adenosine A1 receptor agonist), NECA (adenosine A2 receptor agonist) and 2-ClAd (adenosine A1, A2 receptors agonist). The caffeine-induced seizure was unaffected by diazepam (benzodiazepine receptor agonist), but was inhibited by Ro 15-1788 (antagonist or partial agonist). beta-DMCM (antagonist or inverse agonist) increased the seizure. Muscimol (GABA-a receptor agonist), baclofen (GABA-b receptor agonist) and AOAA (GABA transaminase inhibitor) did not show significant effect on caffeine-induced convulsion. Bicuculline (GABA-a receptor antagonist) and picrotoxin (chloride channel blocker) significantly potentiated the convulsion at the doses which did not induce it. Caffeine-induced convulsion was potentiated by NMDA with its non-convulsive dose. CPP (competitive NMDA receptor antagonist) and MK-801 (non-competitive NMDA receptor antagonist) significantly inhibited the seizures. These results suggest that caffeine-induced seizure is not caused by blockade of adenosine receptors. Caffeine may act to beta-carboline sensitive benzodiazepine receptor (Type 1) which has no linkage with GABA-a receptor. Furthermore, it is implied that caffeine plays some role at NMDA receptor calcium ion channel complex.
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PMID:[Effects of agonists and antagonists of benzodiazepine, GABA and NMDA receptors, on caffeine-induced seizures in mice]. 132 1


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