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1

Digitale Medien

The Effect of Chronic Treatment with the GABA Transaminase Inhibitors γ-Vinyl-GABA and Ethanolamine-O-Sulphate on the In Vivo Release of GABA from Rat Hippocampus (1995)

Qume, M. ; Whitton, P. S. ; Fowler, L. J.

Oxford, UK : Blackwell Science Ltd

Journal of neurochemistry 64 (1995), S. 0

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ISSN: 1471-4159

Quelle: Blackwell Publishing Journal Backfiles 1879-2005

Thema: Medizin

Notizen: Abstract: The effects of chronic treatment with the specific, mechanism-based, irreversible inhibitors of 4-aminobutyrate aminotransferase (EC 2.6.1.19; GABA transaminase), ethanolamine O-sulphate (EOS), and 4-aminohexenoate [vigabatrin; γ-vinyl-GABA (GVG)] on the extracellular concentrations of GABA in the hippocampus have been studied using in vivo microdialysis in conscious animals. Oral dosing [3 mg/ml of drinking water, giving doses of GVG of 194 ± 38 mg/kg/day and of EOS of 303 ± 42 mg/kg/day (mean ± SD)] was followed by microdialysis at 2, 8, and 21 days. The basal outflow of GABA (in the range of ∼1–2 pmol/30 µl/30-min sample) after 2 and 8 days of treatment was not significantly different from that in control animals, but the 21-day treatment gave significant rises in the extracellular GABA concentration (up to ∼6–8 pmol/30 µl/30-min sample). Both inhibitors gave similar results. Depolarisation with 100 mM K+ gave large increases in GABA release in control (∼20–60 pmol/30 µl/30-min sample) and treated animals. The 8- and 21-day-treated animals showed significant increases in the stimulated release compared with control animals (∼80–100 pmol/30 µl/30-min sample). Excluding Ca2+ had no significant effect on either basal or stimulated release. The significant increases in K+-evoked release of GABA show that the increased intracellular pool of GABA is available for release, and this may be related to the anticonvulsant action of these compounds.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1046/j.1471-4159.1995.64052256.x

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2

Digitale Medien

Regional Effects of Sodium Valproate on Extracellular Concentrations of 5-Hydroxytryptamine, Dopamine, and Their Metabolites in the Rat Brain: An In Vivo Microdialysis Study (1992)

Biggs, C. S. ; Pearce, B. R. ; Fowler, L. J. ; [weitere]

Oxford, UK : Blackwell Publishing Ltd

Journal of neurochemistry 59 (1992), S. 0

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ISSN: 1471-4159

Quelle: Blackwell Publishing Journal Backfiles 1879-2005

Thema: Medizin

Notizen: Abstract: The effects of sodium valproate (VPA; 100, 200, and 400 mg/kg, i.p.) on ventral hippocampal and anterior caudate putamen extracellular levels ofdopamine (DA) and 5-hydroxytryptamine (5-HT) were examined using in vivo microdialysis. VPA induced dose-related increases in dialysate DA, 3,4-dihydroxyphenylacetic acid, and 5-HT in the ventral hippocampus. Anterior caudate putamen dialysate 5-HT was also dose dependently elevated by the drug, whereas DA levels tended to decrease with increasing VPA dose. In contrast, VPA (200, 400, and 800 mg/kg, i.p.) produced no significant elevation of DA in posterior caudate putamen dialysates, although 5-HT levels were significantly elevated at the 400- and 800-mg/kg doses. In all three regions studied, dialysate concentrations of 5-hydroxyindoleacetic acid and homovanillic acid remained at basal levels following VPA treatments. The results are discussed with regard to the possible anticonvulsant mode of action of VPA.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1111/j.1471-4159.1992.tb11001.x

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3

Digitale Medien

Tetanus Toxin-Induced Effects on Extracellular Amino Acid Levels in Rat Hippocampus: An In Vivo Microdialysis Study (1996)

Britton, P. ; Whitton, P. S. ; Fowler, L. J. ; [weitere]

Oxford, UK : Blackwell Science Ltd

Journal of neurochemistry 67 (1996), S. 0

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ISSN: 1471-4159

Quelle: Blackwell Publishing Journal Backfiles 1879-2005

Thema: Medizin

Notizen: Abstract: Tetanus toxin is a potent neurotoxin that is widely considered to produce its effect through impairment of inhibitory neurotransmission. We report the effect of a single unilateral intrahippocampal injection of tetanus toxin on extracellular levels of neuroactive amino acids in freely moving rats, at times ranging between 1 and 7 days posttreatment. Tetanus toxin treatment did not alter extracellular levels of aspartate, glutamate, and taurine at any time during the study. However, although extracellular GABA levels were unaffected by toxin injection 1, 2, and 3 days after treatment, they were reduced (45 ± 8% of contralateral vehicle-injected level) at day 7. Challenge with a high K+ concentration, 7 days after treatment, produced elevations in extracellular levels of taurine and GABA in both vehicle- and toxin-injected hippocampi, with evoked levels of GABA being lower in the toxin-treated side (39 ± 16% of contralateral vehicle-injected level). Aspartate and glutamate levels were not increased by high-K+ infusion. These findings are discussed in relation to the possible role that an imbalance in excitatory/inhibitory tone may play in the production of tetanus toxin-induced neurodegeneration.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1046/j.1471-4159.1996.67010324.x

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4

Digitale Medien

Putative Neurotoxicity of SKF 38393 and Other D1 Dopaminergic Drugs Investigated in Rat Striatum (1992)

Isaac, L. ; Mills, R. ; Fowler, L. J. ; [weitere]

Oxford, UK : Blackwell Publishing Ltd

Journal of neurochemistry 58 (1992), S. 0

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ISSN: 1471-4159

Quelle: Blackwell Publishing Journal Backfiles 1879-2005

Thema: Medizin

Notizen: Abstract: The recently alleged neurotoxicity of the D1 receptor agonist, SKF 38393, was investigated in rat striatum by measuring the enzymes acetylcholinesterase (AChE) and glutamate decarboxylase (GAD). First, unilateral intrastriatal microinjection of the excitotoxin kainic acid (2 μg in 1 μ1) was shown to evoke vigorous contraversive circling, followed 1 or 2 weeks later by profound decreases in striatal AChE (24 and 54%), GAD (51 and 75%), and protein (36 and 47%), as well as loss of GAD (45% at 2 weeks) in the ipsilateral substantia nigra. Similar striatal treatments with SKF 38393 (30 μg in 0.5–1 μ), the related benzazepines SKF 82526 (D1 agonist, 30 μg in 1 μ1) and SCH 23390 (D1 antagonist, 5 μg in 1 μ1), or the phenanthridine D1 agonist CY 208-243 (5 μg in 1 μ1) failed to affect the rats' behaviour or their striatal levels of AChE, GAD, and protein. Intrastriatal SKF 38393 (30 μg in 0.5 μ1) also had no influence on these enzymes in the substantia nigra. It is concluded that none of the D1 dopaminergic compounds examined here was neurotoxic toward the many different cell groups that contain AChE and/or GAD in the striatum.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1111/j.1471-4159.1992.tb11365.x

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5

Digitale Medien

MK-801 Increases Extracellular 5-Hydroxytryptamine in Rat Hippocampus and Striatum In Vivo (1992)

Whitton, P. S. ; Biggs, C. S. ; Pearce, B. R. ; [weitere]

Oxford, UK : Blackwell Publishing Ltd

Journal of neurochemistry 58 (1992), S. 0

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ISSN: 1471-4159

Quelle: Blackwell Publishing Journal Backfiles 1879-2005

Thema: Medizin

Notizen: Abstract: The effect of MK-801 (0.25 or 0.5 mg/kg) on the extracellular concentration of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in rat hippocampus and striatum was studied using intracerebral dialysis. The dialysate 5-HT concentration was dose-dependently increased by MK-801 in both regions. In the hippocampus, at the higher drug dose a slow increase in the 5-HIAA level was observed, and this became significant 3 h after treatment. In contrast to this, the extracellular 5-HIAA content in the striatum was significantly decreased 150 min after administration of both doses of MK-801. The data are discussed in the light of the known behavioural effects of MK-801 and possible N-methyl-d-aspartic acid receptor regulation of 5-HT release.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1111/j.1471-4159.1992.tb11381.x

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6

Digitale Medien

ANALYSIS OF THE MAJOR AMINO ACIDS OF RAT BRAIN AFTER IN VIVO INHIBITION OF GABA TRANSAMINASE BY ETHANOLAMINE O-SULPHATE (1973)

Fowler, L. J.

Oxford, UK : Blackwell Publishing Ltd

Journal of neurochemistry 21 (1973), S. 0

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ISSN: 1471-4159

Quelle: Blackwell Publishing Journal Backfiles 1879-2005

Thema: Medizin

Notizen: The effect of in vivo inhibition of GABA transaminase by ethanolamine O-sulphate on the content of the free amino acids in rat brain has been studied. Intracisternal injection of 2.0 mg/kg resulted in a progressive increase in GABA levels with time, to reach after 8 h a 100 per cent increase over saline-injected control animals. The effect of injection of 0.5, 1.0 and 2.0 mg/kg was studied 24 h after injection and the results showed that the increased GABA levels were dependent on the dose of inhibitor employed. Apart from the substantial increase in the GABA concentration of the brain there were no significant changes in the content of the other amino acids except for a small but significant decrease in aspartic acid in one experiment. When the extent of inhibition of the transaminase was correlated with the rise in GABA concentration it was shown that no elevation occurred until more than half of the enzymic activity had been inhibited.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1111/j.1471-4159.1973.tb04263.x

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