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

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

GABAergic modulation of enkephalin, substance P and glutamic acid decarboxylase (GAD67) gene expression and the alterations induced by dopamine receptor blockade were studied in the rat striatum. Following subchronic treatment with the GABA-A agonist muscimol, the GABA-B agonist baclofen or the GABA transaminase inhibitor gamma-vinyl GABA there were no significant changes in striatal peptide and GAD67 gene expression. Following repeated administration of the D-2 antagonists, eticlopride and haloperidol, there was an increase in enkephalin and GAD67 mRNA levels and parallel decrease in that of substance P. These were unaffected by co-administration of gamma-vinyl GABA. The D-1 antagonist, SCH 23390 administered alone or together with gamma-vinyl GABA did not alter peptide or GAD67 mRNA levels. It seems that pharmacological stimulation of GABA receptors has little effect on enkephalin, substance P or GAD67 mRNA expression in striatal output neurons.
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PMID:GABAergic modulation of striatal peptide expression in rats and the alterations induced by dopamine antagonist treatment. 753 10

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