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 raphe nuclei [which contain serotonin (5-HT) cell bodies] are also known to contain axons that store substance P, met-enkephalin, and gamma-aminobutyric acid (GABA). We have previously shown that GABA has a tonic inhibitory action on 5-HT turnover. To examine other possible interactions of these neuronal systems, we assessed the effect on 5-HT turnover of injecting substance P and 2-D-ala-met-enkephalin into the median raphe nucleus, and the effects of substance P on GABA turnover. Serotonin turnover was increased by 30% in the hippocampus after the injection of substance P (4 micrograms) into the median raphe, indicating an excitatory effect of substance P on the raphe-hippocampal system. Local injection of the metabolically stable metenkephalin analog 2-D-ala-met-enkephalin amide (10 micrograms) increased the hippocampal steady state content of 5-hydroxyindoleacetic acid (5-HIAA) by 60%. The data suggest an excitatory effect of met-enkephalin within the raphe nucleus. We attempted to estimate GABA turnover from the rate of disappearance of GABA after inhibition of glutamic acid decarboxylase by isoniazid and by the rate of accumulation of GABA after inhibition of GABA transaminase by gabaculine. Isoniazid, which is a competitive inhibitor, had too short and incomplete an action to be of use when injected intranuclearly. Gabaculine, which is an irreversible inhibitor, induced a rapid-onset increase in GABA content. This accumulation was linear up to 90 min. The injection fo gabaculine (80 ng) into the raphe increased GABA content by five times the control values, but hippocampal 5-HT and 5-HIAA contents were not significantly changed. Substance P injection increased the GABA turnover by 30%. Gabaculine seems a promising tool for detecting changes in GABA turnover.
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PMID:Serotonin and gamma-aminobutyric acid turnover after injection into the median raphe of substance P and D-ala-met-enkephalin amide. 617 97

beta-Endorphin, Met-enkephalin, substance P, and somatostatin concentrations were evaluated in the hypothalami of rats treated either acutely or chronically (15 days) with sodium valproate, diphenylhydantoin, phenobarbital, or ethosuximide. All of these drugs, with the exception of ethosuximide, induced significant decreases in beta-endorphin concentrations after acute treatment, while only sodium valproate induced a decrease after chronic treatment. The acute and chronic effects of sodium valproate were also produced by aminooxyacetic acid, an inhibitor of gamma-aminobutyric acid (GABA) transaminase, while another GABA transaminase inhibitor, ethanolamine-O-sulphate, and THIP, a GABA receptor agonist, were effective after acute administration. Metenkephalin, substance P, and somatostatin concentrations were never affected by the drugs used. The present results, indicating that antiepileptic agents specifically decrease beta-endorphin concentrations, seem to correlate well with the capacity of these agents to blunt the epileptic activity of the peptides tested. Moreover, our data suggest that GABA may be involved in the anticonvulsant-induced reduction of beta-endorphin concentrations.
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PMID:Antiepileptic agents affect hypothalamic beta-endorphin concentrations. 620 24

Uptake, synthesis, storage, and release of gamma-aminobutyric acid (GABA) are some of the characteristic properties of GABA-ergic neurons. In the present study, we have used these properties as physiological probes to follow the emergence and maturation of GABA-ergic neurons during postnatal development of the rabbit retina. There is autoradiographic, immunocytochemical, and pharmacological evidence that some amacrine cells and certain neurons in the ganglion cell layer probably use GABA as the neurotransmitter. These neurons take up GABA, contain the GABA-synthesizing enzyme L-glutamic acid decarboxylase (GAD, EC 4.1.1.15), and release the accumulated GABA by a CA++-dependent mechanism when depolorized with high extracellular K+ concentration. In this study, we show that certain neurons in the newborn retina already possess a specific mechanism for GABA uptake. The positions and numbers of these cells in the developing retina suggest that they will become GABA-ergic neurons in the adult retina. These putative GABA-ergic neurons are, however, probably immature at birth because newborn retinas contain only low levels of GABA and GAD. Additionally, there is relatively little K+-stimulated, Ca++-dependent release of (3H)-GABA from the newborn retinas. GABA concentrations and GAD activities in developing retinas increase steadily postnatally, reaching about 80% of the adult levels by day 9. The activities of the GABA-degrading enzyme, GABA-glutamate transaminase (GABA-T, EC 2.6.1.19), follow a similar pattern of maturation during retinal development. K+ stimulated GABA release, however, remains low until about day 6, and then increases dramatically from 20% to 85% of the adult level over the next 3 days. Taken together, our results indicate that in the rabbit retina, the commitment by certain neurons to use GABA as the transmitter is made prenatally. These neurons are immature at birth but are biochemically, physiologically, and probably functionally mature by about 9 days after birth.
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PMID:Postnatal development of GABA-ergic neurons in the rabbit retina. 625 33

gamma-Acetylenic GABA (GAG, RMI 71.645), a potent irreversible inhibitor of gamma-aminobutyric acid transaminase, was given orally in various dosage schedules to 14 patients with Huntington disease. The biochemical effects of the drug on cerebrospinal fluid (CSF) concentrations of gamma-aminobutyric acid (GABA) and the GABA-containing dipeptide, homocarnosine, were measured in 10 of 14 patients. Treatment with GAG increased CSF concentrations of GABA and homocarnosine as compared to pretreatment values, suggesting that the drug increased brain GABA concentration. Despite this neurochemical effect, the clinical state was not improved. Except for single seizure episodes in five patients, GAG therapy was well tolerated. These results do not exclude the possibility that agents that augment CNS GABAergic function may prove useful in therapy of Huntington disease.
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PMID:Treatment of Huntington disease with gamma-acetylenic GABA an irreversible inhibitor of GABA-transaminase: increased CSF GABA and homocarnosine without clinical amelioration. 625 6

Intraperitoneal injection of ethanol (1-2 g/kg) and chlordiazepoxide (2-16 mg/kg) suppressed susceptibility to audiogenically induced, clonic-tonic seizures and antagonized forelimb tremor in rats undergoing ethanol withdrawal, 30 min after treatment. However, a smaller dose of ethanol (0.5 g/kg) actually increased clonic seizure frequency, suggesting that ethanol exerts a biphasic proconvulsant/anticonvulsant action. Direct activation of gamma-aminobutyric acid (GABA) receptors by intracisternal administration of GABA (100-1000 micrograms), muscimol (0.3-1.0 micrograms) or 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) (0.3-3.0 micrograms) 5 to 10 min before testing also reduced susceptibility to audiogenic clonic-tonic seizures. In sharp contrast to these anticonvulsant actions, GABA, muscimol and THIP had no effect on withdrawal-induced forelimb tremors. Blockade of GABA uptake with 1-2,4-diaminobutyric acid (300 and 600 mg/kg i.p.) and inhibition of GABA transaminase with aminooxyacetic acid (12.5 and 25.0 mg/kg i.p.) both reduced susceptibility to seizures. However, anticonvulsant doses of these two drugs, unlike GABA, muscimol and THIP, also reduced forelimb tremor. Three other GABA transaminase inhibitors, gamma-vinyl GABA (450 and 900 mg/kg i.p.), gamma-acetylenic GABA (50-150 mg/kg i.p.) and ethanolamine-O-sulfate (250-750 mg/kg i.p.), were inactive against ethanol withdrawal audiogenic seizures and forelimb tremors. These results indicate that direct GABA receptor activation can selectively suppress one type of ethanol withdrawal response (i.e., audiogenic seizure susceptibility) while failing to influence another (forelimb tremors).
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PMID:Differential sensitivity of ethanol withdrawal signs in the rat to gamma-aminobutyric acid (GABA)mimetics: blockade of audiogenic seizures but not forelimb tremors. 631 80

One of the defects in human epilepsy appears to be the suboptimal functioning of at least certain central gamma-aminobutyric acid (GABA)-mediated synapses. Of the several approaches for the manipulation of the functional state of such synapses that have been investigated, the possibility of interference with GABA metabolism and GABA transport processes is reviewed. It is concluded that the efficiency of inhibitors of the GABA-metabolizing enzyme, GABA transaminase, as antiepileptic drugs is related to the ability of the inhibitors to increase selectively the synaptic or transmitter-related GABA levels. Whether or not this reflects different modes of action of these inhibitors on neuronal and glial GABA transaminase remains to be established. Inhibition of the GABA transport mechanisms seems to represent an alternative approach to increase synaptic GABA levels. Evidence is presented that inhibitors of glial GABA uptake possess anticonvulsant activity. A comparison of drugs that inhibit both neuronal and glial GABA uptake with selective glial GABA uptake inhibitors indicates that the latter type of inhibitor most effectively blocks seizure activity. Such a drug is 4,5,6,7-tetrahydroisoxazolo[4,5c]pyridin-3-ol (THPO), which unfortunately lacks the important property of easy penetration of the blood-brain barrier. Prodrugs of this glial-selective GABA uptake inhibitor may have pharmacological and therapeutic interest.
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PMID:Transport and metabolism of gamma-aminobutyric acid in neurons and glia: implications for epilepsy. 631 24

To clarify the role and site of action of gamma-aminobutyric acid (GABA) in ovine pineal glands, we have investigated the effects of aminooxyacetic acid (AOAA), an inhibitor of GABA transaminase, on endogenous GABA content and beta-adrenoceptor mediated pineal function in Merino sheep. A significant elevation of endogenous GABA levels was noted in the glands, but no effect was observed on radioligand binding in vitro to pineal beta-adrenoceptors following in vivo administration of AOAA. Incubation of washed pineal membranes with GABA or AOAA had no effect on ligand binding to beta-adrenoceptors. Incubation of Merino pineal slices with GABA inhibited isoprenaline-stimulated but not basal serotonin N-acetyltransferase (NAT) activity. Incubation of whole pineal homogenates with GABA was without effect on either isoprenaline-stimulated or basal adenyl cyclase activity. Thus, Merino pineal glands resemble bovine pineals in that beta-adrenoceptor mediated melatonin biosynthesis in both species may be regulated in part by GABA. Our results indicate that GABA may exert its effect on Merino pineal NAT activity at a locus distal to the site of action of adenyl cyclase; however, the detailed mechanism and physiological role of this regulation remain to be elucidated.
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PMID:Sheep pineal beta-adrenoceptor function--interaction with gamma-aminobutyric acid. 632 80

Histochemical and biochemical studies demonstrate that gamma-aminobutyric acid (GABA), glutamic acid decarboxylase (EC 4.1.1.15), and GABA aminotransferase (EC 2.6.1.19) are present in bovine adrenal chromaffin cells. Moreover, [3H]GABA can be taken up and stored by primary cultures of adrenal chromaffin cells. Nicotinic receptor stimulation or KCl depolarization releases the [3H]GABA taken up by these cell cultures. GABA and benzodiazepine recognition sites located in chromaffin cells interact with each other with modalities similar to those described for GABA and benzodiazepine recognition sites located in synaptic membranes prepared from brain tissue. Bicuculline facilitates the release of catecholamine from chromaffin cells induced by nicotinic receptor stimulation but it fails to influence the release of catecholamine evoked by K+ depolarization. Since the GABA-benzodiazepine receptor system appears to modulate nicotinic receptor function, it is suggested that GABA transmission might participate in modulating responsiveness of chromaffin cells to incoming cholinergic stimuli.
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PMID:Intrinsic GABAergic system of adrenal chromaffin cells. 632 6

The present experiment was undertaken to investigate the possible involvement of GABAergic neurons in the regulation of the feeding behavior induced by tail pinching. Injections before the tail pinching of gamma-aminobutyric acid (GABA) agonist (Muscimol: 570 micrograms.kg-1 i.p. 20 min before testing), GABA antagonist (Picrotoxine: 1,5 mg.kg-1 i.p. 30 min before testing) and a GABA transaminase inhibitor (Acetate dipropyle: 200 mg.kg-1 i.p. 40 min before testing) have no effects on the ingestion of sweet milk. These preliminary results provide support for the hypothesis that the feeding behavior induced by TP is not mediated through GABAergic system.
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PMID:[Influence of the GABAergic system on eating behavior induced by the tail pinching technic in rats]. 645 43

The anticonvulsant effect of inhibitors of GABA-T (R/S-gamma-vinyl-GABA, ethanolamine-O-sulfate, gabaculine, aminooxyacetic acid) was enhanced by 10 mmol/kg glycine in animal seizure models which are based on a functional GABA deficit. Similar to glycine in their action, although less effective, were its close structural analogues (sarcosine, N,N-dimethylglycine) and homologous omega-aminoacids (beta-alanine, taurine, gamma-aminobutyric acid, delta-aminovaleric acid). It is assumed that glycine and its structural analogues act on supraspinal glycine receptors as glycine agonists. Our observation is the first example of the synergistic interaction of two inhibitory neuronal systems resulting in the amplification of the anticonvulsant effect. Combined treatment with GABA-T inhibitors and glycine may turn out to be of practical importance in the therapy of seizure disorders and other diseases, for which treatment with GABA-T inhibitors is considered a potentially useful therapeutic approach.
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PMID:Synergistic anticonvulsant effects of GABA-T inhibitors and glycine. 647 85


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