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 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

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

Effects of drugs which enhance or reduce GABAergic neurotransmission upon conflict behavior were evaluated with a modified Vogel procedure which was shown to be insensitive to variations in motivation to drink and to the analgesic effects of morphine. In addition, the effects of these drugs on ambulatory activity and motor execution were quantified. For comparison, the benzodiazepines diazepam and chlordiazepoxide were used. Anticonflict actions of diazepam were obtained with a shock current of 0.25 mA but not with 0.05 or 0.5 mA, whereas the proconflict effect of FG7142 was obtained with 0.05 mA but not with higher currents. Diazepam and chlordiazepoxide had anxiolytic effect in a dose similar to that required to reduce ambulatory activity, but below that needed to affect motor execution. At doses high enough to impair motor execution, anticonflict effects were considerable. The GABA-A receptor agonist THIP and the GABA-B receptor agonist baclofen lacked effect on conflict behavior in moderate doses, which reduced ambulatory activity. In doses which produced motor deficiencies these drugs reduced licking both in the conflict test and when tested without shock administration. The effects of the GABA transaminase inhibitors gamma-acetylene GABA and sodium valproate were similar to those of the receptor agonists. The GABA reuptake inhibitor SKF 100330A produced anticonflict effect in a dose below that needed to reduce ambulatory activity, but lacked effect on conflict behavior in higher doses. The GABA antagonist picrotoxin, and the GABA synthesis inhibitors 4-deoxypyridoxine and isoniazide, reduced licking both in the absence and presence of shock, and affected motor functions in the same doses. Bicuculline, at the doses used, had no behavioral effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GABAergic drugs and conflict behavior in the rat: lack of similarities with the actions of benzodiazepines. 166 Jan 3

The role of GABAergic neuronal system in learning and memory was investigated using the step-down typed passive avoidance and rapidly learned conditioned suppression tasks in mice. GABA antagonists, picrotoxin and bicuculline, or a GABA synthesis inhibitor, 3-mercaptopropionic acid (3-MP), were administered just after the training test. All of these drugs caused amnesia: they shortened the step-down latency (SDL) and attenuated the conditioned suppression of motility in the retention test conducted 24 h after the administration. Furthermore, we investigated the effect of GABA receptor agonists, muscimol and baclofen, or a GABA transaminase inhibitor, aminooxyacetic acid (AOAA), on these amnesia models. GABA agonists showed an antiamnesic action as follows: in the passive avoidance task, 1) picrotoxin-induced amnesia was antagonized by muscimol, baclofen and AOAA. 2) Bicuculline-induced amnesia was antagonized by muscimol and AOAA but not by baclofen. 3) 3-MP-induced amnesia was antagonized only by muscimol. 4) In the rapidly learned conditioned suppression task, picrotoxin-, bicuculline- and 3-MP-induced amnesia were antagonized by muscimol, baclofen and AOAA. These results suggest that the GABAergic neuronal system plays an important role in the memory retention of passive avoidance and rapidly learned conditioned suppression tasks.
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PMID:GABAergic modulation of memory with regard to passive avoidance and conditioned suppression task in mice. 312 29

Previous studies have suggested that gamma-aminobutyric acid (GABA) exerts inhibitory actions on luteinizing hormone (LH) secretion that are likely to be mediated by modifications in noradrenergic transmission. To explore further this hypothesis we have studied the effect of increasing GABA contents in discrete areas of the brain on plasma LH levels in short-term orchidectomized rats. GABA accumulation was produced by the GABA transaminase inhibitor, gamma-vinyl-GABA (GVG). The locus coeruleus area (LC), where the noradrenaline (NA) cells projecting through the dorsal noradrenergic bundle are located, and several hypothalamic areas that are innervated by NA-containing fibers were microinjected with GVG. Most of these areas are known to be related to the neural control of LH secretion. GVG microinjected in the LC and medial preoptic area increased the GABA content and blunted significantly the acute increase of plasma LH produced by castration. Bicuculline prevented these effects. Delayed effects of GVG were observed when applied in the anterior hypothalamic area and ventromedial-arcuate nucleus area. In these latter areas, a single injection of GVG did not augment the GABA concentrations and was unable to prevent LH release, but a clear inhibitory effect took place after a second injection of GVG between 24 and 48 h after orchidectomy. Unresponsive areas to GVG treatment were the lateral preoptic area, the median eminence and the dorsal raphe. These results add support to the view that GABA inhibits LH release in rats, at discrete areas of the brain.
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PMID:Localized increase of GABA levels in brain areas of the rat and inhibition of the plasma LH rise following orchidectomy. 322 82

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

Behavioural effects following bilateral intranigral administration of GABA antagonists have been investigated. Bicuculline methiodide (BMI), picrotoxin and isopropylbicyclophosphate all induced biting behaviour, teeth-chattering and chewing. Sub-threshold doses for biting induced locomotor activity and sniffing. The strongest response was observed after injection into the caudal pars reticulata, whereas weaker effects were seen after injection into the rostral pars reticulata or the pars compacta. The biting induced by intranigral BMI was not antagonized by prior catecholamine depletion with reserpine plus alpha-methyl-p-tyrosine or by dopamine receptor blockade with haloperido. Concomitant intranigral injection of the GABA agonists muscimol and THIP, however, completely antagonized biting. Systemic GABAergic drugs also antagonized the BMI-induced biting: the benzodiazepine, diazepam and the GABA transaminase inhibitor, gamma-acetylenic GABE, were most effective, whereas muscimol was only partially effective and THIP was without effect. It is suggested that this animal model may be used for the evaluation of antidyskinetic drugs.
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PMID:Intranigral GABA antagonists produce dopamine-independent biting in rats. 718 66

1. The GABA transaminase inhibitor and activator of glutamic acid decarboxylase, valproic acid is being used for the treatment of migraine. Its mechanism of action is unknown. We tested the effects of sodium valproate and GABAA-agonist muscimol on dural plasma protein ([125I]-bovine serum albumin) extravasation evoked by either unilateral trigeminal ganglion stimulation (0.6 mA, 5 ms, 5 Hz, 5 min) or substance P (SP) administration (1 nmol kg-1,i.v.) in anaesthetized Sprague-Dawley rats. 2. Intraperitoneal (i.p.) injection of sodium valproate or muscimol, but not baclofen (< or = 10 mg kg-1, i.p.) dose-dependently reduced dural plasma protein extravasation caused either by electrical trigeminal stimulation (ED50: 6.6 +/- 1.4 mg kg-1, i.p., and 58 +/- 18 micrograms kg-1, i.p. for valproate or muscimol, respectively) or by intravenous substance P administration (ED50: 3.2 +/- 1.4 mg kg-1, i.p. and 385 +/- 190 micrograms kg-1, i.p. for valproate or muscimol, respectively). 3. Valproate (6.6 mg kg-1, i.p.) or muscimol (58 micrograms kg-1, i.p.) had no effect on mean arterial blood pressure or heart rate when measured for 30 min after i.p. administration. 4. The GABAA-antagonist bicuculline (0.01 mg kg-1, i.p.) completely reversed the effect of valproate and muscimol on plasma extravasation following electrical stimulation or substance P administration, whereas the GABAB-receptor antagonist, phaclofen (0.01-1 mg kg-1, i.p.) did not. Bicuculline or phaclofen, given alone, did not alter the plasma extravasation response after either electrical stimulation or SP administration. 5. Valproate decreased plasma extravasation following substance P administration in adult animals, neonatally treated with capsaicin by a bicuculline-reversible mechanism. This suggests that GABAA receptors are not found primarily on those afferent neurones or fibres which are sensitive to capsaicin treatment in neonatal rats.6. We conclude that sodium valproate blocks plasma extravasation in the meninges through GABAA mediated postjunctional receptors probably within the meninges. The dosages required are comparable to those used clinically. Agonists and modulators at the GABAA receptor may become useful for the development of selective therapeutic agents for migraine and cluster headache.
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PMID:Peripheral GABAA receptor-mediated effects of sodium valproate on dural plasma protein extravasation to substance P and trigeminal stimulation. 856 34