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)

Differences in the kinetic properties of brain gamma-aminobutyrate aminotransferase (GABA-transaminase; GABA-T) in different species are described in the present investigation. In both rat and human brain enzymes, the effect of temperature on the activity was studied. The maximal activity, for a 30-min incubation period, was attained at an incubation temperature of 45 degrees C for rat and 56 degrees C for human brain tissue. The addition of plasma or plasma proteins was found to induce a two-fold increase of the activity of rat brain GABA-T, whereas a slight inhibitory effect on human brain enzyme and no effect on mouse brain enzyme was observed. The species differences are shown to be the results of differences in the binding of the cofactor pyridoxal phosphate to the apoprotein, which are revealed when the free concentration of pyridoxal phosphate is reduced by binding to serum albumin.
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PMID:Studies on gamma-aminobutyrate aminotransferase (GABA-T) activities in human and rodent brain homogenates. 128 90

The postembedding immunogold procedure was used to detect changes in the levels of gamma-aminobutyric acid (GABA)-like immunoreactivity at the ultrastructural level in the cerebellar cortex of control rats and rats treated with the GABA transaminase inhibitor, amino-oxyacetic acid (AOAA), in order to increase the levels of GABA. GABA-immunoreactive structures were labelled using an antiserum directed against GABA coupled to bovine serum albumin and a secondary antibody conjugated to colloidal gold. The density of gold particles per square micron of tissue was taken as a measure of GABA-like immunoreactivity. In separate groups of control and AOAA-treated animals, the levels of GABA were assessed biochemically in the cerebellum, the cortex, the ventral mesencephalon and the striatum. Six hours after treatment with AOAA the GABA levels in the cerebellum, the cortex, the ventral mesencephalon and the striatum. Six hours after treatment with GABA immunoreactivity of the Golgi and basket cell terminals was significantly greater than that of mossy fibres, granule cell dendrites and perikarya and glial cells. The value obtained for Golgi terminals was the highest of all the structures examined and was twice that of their perikarya. Six hours after treatment with AOAA the GABA immunoreactivity in Golgi and basket cell terminals and in glial cells was greatly enhanced. The drug treatment slightly enhanced the immunoreactivity in mossy fibres and granule cell dendrites but induced no change in granule cell bodies. Thus, in both control and treated rats, the highest GABA immunoreactivity was present in the terminals of GABAergic cells, and the lowest in putative glutamatergic cells. The results demonstrate that there is a high degree of selectivity in the changes in GABA levels following the inhibition of GABA transaminase in the cerebellum. They also confirm the potential of the use of postembedding methods for the quantification of endogenous amino acid at cellular and subcellular levels, in relative and possibly also absolute terms.
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PMID:GABA-like immunoreactivity in different cellular populations of cerebellar cortex of rats before and after treatment with amino-oxyacetic acid. 205 35

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