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)

Three different micromethods for studying GABA biochemistry and function at single microdissected GABA-acceptive neuronal membranes are discussed. The basis for such studies is the possibility of obtaining by microdissection single Deiters' neurons from the lateral vestibular nucleus of the rat and the rabbit. From these isolated cells the plasma membrane may be prepared and studied. The first micromethod allows the study of the Na+ independent diffusion of GABA through such a plasma membrane which is postsynaptic to GABA-ergic boutons. A modification of such method allows also the study of the effects of GABA-ergic drugs on Cl- permeability. The second method allows the study by microelectrophoresis in capillaries of GABA catabolism by GABA-T associated with microdissected single Deiters' membranes. The third one was developed in order to study the characteristics of Na+ dependent GABA carrier activity present on such membranes.
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PMID:Micromethods for the study of GABA biochemistry and function at single GABA acceptive membranes. 367 87

The influence of 2-(2-oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1, 1-dioxide (supidimide), a representative of a new class of sedative drugs, on the noradrenergic, dopaminergic, serotoninergic and gamma-aminobutyric acid (GABA)ergic neuronal systems of rodent brains was investigated. In each case the brain transmitter levels after administration of supidimide were determined. Utilisation of noradrenaline (norepinephrine, NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) was also investigated ex vivo. The study was complemented with in vitro investigations of biosynthesis, synaptosomal uptake, degradation, and receptor binding of the transmitters. Based on a preliminary study of the distribution of [35S]-supidimide in rat brain, in vitro effects observed at greater than 10(-4) mol/l were considered irrelevant. Similarly, in vivo effects requiring dosages higher than 300 mg/kg i.p. were not regarded adequate to explain the sedative and antiaggressive efficacy of supidimide. With the above restrictions, the following parameters can be rated as not influenced by supidimide: levels of tryptophan in rat brain and serum (free and total); 5-HT biosynthesis in vivo (rat brain; 5-HT accumulation after monoamine oxidase (MAO) blockade); activity of MAO-A and MAO-B (rat brain mitochondria); uptake of 5-HT, NE and DA (rat synaptosomes); 5-HT receptor binding ( [3H]-LSD binding assay in rat cortical membranes); tyrosine hydroxylase activity (rat adrenal glands); catechol-O-methyl transferase (COMT) (rat liver); NE binding to central alpha 1- and alpha 2-receptors (rat brain; radioligand assay with [3H]-dihydroergocryptine, [3H]-prazosin and [3H]-WB 4101 (2',6'-dimethoxy-(G-3H]-phenoxy]-ethylaminomethylbenzo-1,4-dioxane ); DA levels (whole rat brain and striata); dihydroxyphenylacetic acid (DOPAC) levels (whole rat brain without cerebellum and striata); elevated DOPAC levels after pretreatment with haloperidol; DA-dependent adenylate cyclase in vitro (rat striatum); D2 receptor binding ( [3H]-spiperone binding assay, rat striatum); GABA levels (mouse brain); GABA transaminase activity (mouse brain stem); sodium-independent [3H]-GABA receptor binding (rat brain) and benzodiazepine binding (rat cortical membranes, [3H]-diazepam binding assay). Two effects on the GABAergic system were induced by supidimide. Starting at 300 mg/kg i.p., supidimide slowed down the GABA accumulation in brains of aminooxyacetate-treated mice. At 10(-4) mol/l supidimide caused a significant inhibition of GABA uptake (rat synaptosomes).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Influence of supidimide on brain neurotransmitter systems of rats and mice. 608 11

Neuropharmacological mechanisms in central regulation of respiration in anesthetized rats were studied in a whole body plethysmographic model. Neurotransmitter agonists and antagonists were administered intracerebroventricularly or locally into the brain and the respiratory pattern was analysed. The four anesthetics: enflurance (E), halothane (H), pentobarbital sodium (P) and urethane (U) were found to have different effects on central respiratory regulation. Respiratory frequency was higher after H and U compared to after E and P. Animals anesthetized with H exhibited a lower inspiratory drive and a slightly depressed sensitivity to CO2. The responses to the neuropeptides substance P and TRH as well as the amino acid neurotransmitter GABA were partly modified after the different forms of anesthesia. Apomorphine (i.c.v) induced a biphasic, haloperidol reversible, respiratory response in H- and U- (but not in E- and P-) anesthetized rats. The initial bradypnoic response might be due to a decreased sensitivity to afferent vagal signals, while the following tachypnoic phase might be elicited by dopaminergic mechanisms at posterior diencephalic and upper midbrain levels (hypoxic, hypercapnic tachypnea). The tachypnoic response was inhibited by a graded exposure to CO2. The effects of different neurotransmitters were further analysed in H-anesthetized animals. GABA and the GABA agonist muscimol exerted a depressant effect on ventilation in contrast to the GABA-like drugs GHBA an baclofen. Exogenous GABA depressed all respiratory parameters studied exept for inspiratory time and was found to affect mainly respiratory timing mechanisms. An increase in endogenous GABA levels induced by the GABA transaminase inhibitor AOAA blunted the respiratory response to CO2 and induced a ventilatory depression similar to that seen after exogenous GABA. A significance correlation between brain stem GABA levels and respiratory duty cycle was found. The tripeptide TRH induced a marked tachypnea due to the extrahypothalamic actions of the peptide. A delay in the response was seen after local injection into the nucleus tractus solitarius and the tachypnea was abolished by CO2 exposure. The ventilatory effects might be elicited by mechanisms similar to those involved in the tachypnoic response to apomorphine. The tachypnea was potentiated by GABA (possibly due to that both agents act on inspiratory off-switch lowering mechanism) and by methylatropine or naloxone (possibly due to secondary pertubation by cholinergic or enkephalinergic mechanisms). A stimulation of ventilation (increase in tidal volume) was seen after substance P (SP) due to an increase in inspiratory drive and o
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PMID:Neuropharmacological aspects of central respiratory regulation. An experimental study in the rat. 620 94

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

The hypothesis that the brain GABA level increase which is induced by a sodium dipropyl acetate treatment arises either through inhibition of succinic semialdehyde dehydrogenase (SSADH), or through inhibition of GABA transaminase by succinic semialdehyde (SSA), has been considered. It appeared that in vivo brain GABA level increase cannot be attributed to SSADH inhibition, and that SSA is not a GABA precursor. It has been shown that SSA is neither in vivo nor in vitro a GABA-transaminase inhibitor. 4-hydroxybenzaldehyde, a potent SSADH inhibitor did not increase GABA level at a dosage which induces a 99% inhibition of SSADH.
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PMID:[Mechanism of action of an anticonvulsant, sodium dipropylacetate]. 645 31

An inhibitor of GABA-T (sodium n-dipropylacetate), a GABA agonist (muscimol hydrobromide) and an inhibitor of GABA uptake (R,S) nipecotic acid amide were administered to DBA/2 isolated aggressive mice throughout three successive daily experimental sessions. Aggressive responses, measured by an automated device, were inhibited by the highest doses of the three drugs in each daily session. At the lowest doses, sodium, n-dipropylacetate and nipecotic acid amide failed to inhibit aggression in the first session while they were effective in the subsequent sessions. Muscimol was effective in the first session but did not differ significantly from saline in the second and third session. The highest doses of these three drugs did not affect spontaneous motor activity, indicating that the observed drug effects are rather specific.
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PMID:Effects of sodium n-dipropylacetate, muscimol hydrobromide and (R,S) nipecotic acid amide on isolation-induced aggressive behavior in mice. 677 2

The effects of drugs that antagonize or potentiate the action of brain gamma-aminobutyric acid (GABA) on shock-induced aggressive behavior in mice were investigated. In previous studies it has been shown that in C57 BL/6 strain shock-induced aggressive behavior is absent up to the 10th week of age and rises to the highest intensity after the 20th week, while at the same ages aggressive responses are lowest or absent in DBA/2 strain. GABA antagonist, picrotoxin and glutamic acid decarboxylase (GAD) inhibitor, D, L-allylglycine induced aggressive responses in non-aggressive 10 week old C57 BL/6 and 20 week old DBA/2 mice. GABA agonist muscimol hydrobromide, and GABA-T inhibitor sodium n-dipropylacetate inhibited aggressive responses in 20 week old C57 BL/6 mice. These effects were not related to changes in shock sensitivity and motor activity. The results strongly suggest that the GABAergic system is involved in the control of shock-induced aggressive behavior in mice and that this control is related to developmental and genetic factors.
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PMID:Involvement of the GABAergic system on shock-induced aggressive behavior in two strains of mice. 678 19

Sodium valproate was injected acutely (400 mg/kg i.p.) into naive and ethanoloamine-O-sulphate chronically pretreated rats and mice, in an attempt to gain further insight into the effects of this anticonvulsant on GABA metabolism. Sodium valproate significantly enhanced the activity of GAD in the medulla and pons, cerebellum and midbrain regions of rats, and partially relieved the suppression of GAD activity caused by chronic GABA-transaminase inhibition in whole mouse brain. In combination with EOS, sodium valproate caused behavioural excitation in mice which was similar to that sometimes seen with high doses of some GABA-T inhibitors. Pretreatment with EOS potentiated the characteristic abstinence behaviour caused by sodium valproate in rats, though no further significant rise in cerebral GABA levels was observed. In view of the neuronal location of GAD, the elevation of cerebral GABA levels at least in part by potentiation of GAD activity could be involved in the mediation of the anticonvulsant activity of sodium valproate.
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PMID:The effects of sodium valproate on gamma-aminobutyrate metabolism and behaviour in naive and ethanolamine-O-sulphate pretreated rats and mice. 681 85

1. The kinetic profile of sodium valproate (VPA) and the GABA levels were studied in discrete brain areas of the rat after an i.p. injection of 200 mg/kg. The results were discussed comparatively with GABA-T and GAD activities reported in the literature. 2. VPA was rapidly distributed in brain areas; its concentrations, its kinetic parameters and the GABA levels after the drug administration were not uniform in the different brain areas studied. 3. The results showed a particular relation of the VPA to the olfactory bulbs; in this specific area the VPA effect on GABA level was stronger; the VPA apparent half life of elimination was longest; the VPA apparent disappearance rate constant was smallest; the initial GABA level was higher; the activities of GABA-T and GAD were higher than in other brain areas studied except the hypothalamus. 4. These data were correlated with the role of the olfactory bulbs in the behaviour of the rodents.
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PMID:Sodium valproate: kinetic profile and effects on GABA levels in various brain areas of the rat. 681 13

Both cis- and trans-3-aminocyclobutane-1-carboxylic acid have been synthesized as conformationally restricted analogs of GABA. The cis isomer displayed weak to moderate GABA-like activity with respect to (1) inhibition of GABA uptake in rat brain minislices, (2) inhibition of sodium-independent binding of GABA to rat brain membranes, (3) activity as a substrate for GABA aminotransferase. and (4) depression of the firing rate of cat spinal neurons in vivo. The trans isomer was less effective on all four assays. The results has been interpreted in terms of the conformational "pinning back" of the polar groups by the cyclobutane ring in the trans GABA analog so that unfavorable steric interactions would occur between one of the methylene groups and a region of steric hindrance at the active sites for particular GABA processes.
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PMID:Cyclobutane analogs of GABA. 738 41


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