The γ‐Aminobutyrate Content of Nerve Endings (Synaptosomes) in Mice After the Intramuscular Injection of γ‐Aminobutyrate‐Elevating Agents: A Possible Role in Anticonvulsant Activity

Wood, J. D.; Russell, M P; Kurylo, E.

doi:10.1111/j.1471-4159.1980.tb12497.x

Cited by 63 publications

(18 citation statements)

References 16 publications

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“…Thus the degree of elevation and values for the synthesis rate of GABA in different brain regions were similar to those obtained by Collins (1972), Pericic et al (1977), Wood et al (1980), Carmona et al (1980 and Bernasconi et 5.14 ± 0.67 (6) 5.20 ± 0.72 (6) 6.43 ± 0.67 (5) 6.60 ± 0.25 (5) 7.50 ± 0.67 (6) 8.50 ± 0.73 (6) 13.18 ± 0.96 (6) 11.60±0.68 (6) 18.40 ± 0.24 (5) 18.18 ± 0.45 (5) 24.80 ± 0.45 (6) al. (1982).…”

Section: Discussionsupporting

confidence: 86%

Inhibition of the rate of GABA synthesis in regions of rat brain following a convulsion

Green

Metz

Minchin

et al. 1987

British J Pharmacology

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The rate of synthesis of γ‐aminobutyric acid (GABA) in the cortex, hippocampus and striatum of rat brain was assessed by measuring the linear rate of accumulation of GABA following injection of amino‐oxyacetic acid (AOAA). Five min after a single electrically induced seizure there was a rise in GABA content in these brain regions and an almost total inhibition of the rate of synthesis. Five min after seizure induced by the inhalant convulsant flurothyl there was no rise in GABA content in these brain regions but a similar marked degree of inhibition of GABA synthesis. Two hours after the convulsion the rate of GABA synthesis had returned to control values in all three brain regions. A single convulsion did not alter the glutamic acid decarboxylase activity in these brain regions either in the absence or presence of added co‐factor (pyridoxal phosphate). Evidence for an inhibition of GABA release following a convulsion which may be associated with the inhibition of GABA synthesis is presented in the following paper.

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Section: Discussionsupporting

confidence: 86%

Inhibition of the rate of GABA synthesis in regions of rat brain following a convulsion

Green

Metz

Minchin

et al. 1987

British J Pharmacology

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“…Although there is convincing evidence in support of a relationship between the excitable state of the brain and the GABA content of nerve ending (Sarhan & Seiler, 1979;Wood et al, 1980;Wood, 1981), and the theory that the onset of seizures induced by various convulsants is associated with a decrease in the content of GABA or an increase in the content of glutamate (Geddes & Wood, 1984), such findings don't stand for hypoglycemic convulsion since both glutamate and GABA were decreased during preconvulsive, convulsive and postconvulsive stages.…”

Section: Discussionmentioning

confidence: 99%

Changes in the Activity of Glutamate Related Enzymes in Cerebral Cortex, During Insulin-Induced Seizures

Abdul-Ghani

Ghneim

El-lati

et al. 1989

International Journal of Neuroscience

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The activity of glutamate related enzymes and the concentration of glutamine, glutamate and gamma-amino n-butyric acid (GABA) were investigated in the cerebral cortex of rats, in different stages of insulin-induced hypoglycemia. Hypoglycemia was produced by intraperitoneal injection of insulin 0.05-100 units per kg body weight. The minimum required dose to produce irreversible severe hypoglycemia was 0.5 units/kg. In 85% of the cases an insulin induced hypoglycemic convulsion, was achieved 130-150 minutes after injection. Blood glucose levels during insulin induced seizures ranged between 8-15 mg%. In the range of 0.5-100 u insulin/kg the degree of hypoglycemia and the onset of convulsions were identical. The concentration of glutamine was significantly reduced during convulsive and postconvulsive stages. Glutamate and GABA concentrations were reduced significantly in all stages of insulin-induced hypoglycemia. The decrease in glutamine concentration was concurrent with an increase in the activity of its degradative enzyme, glutaminase. This was apparent at the preconvulsive, convulsive and postconvulsive stages. The activity of other enzymes related to energy production such as glutamate dehydrogenase (GDH), glutamate transaminase (GPT) and aspartate aminotransferase (AAT) were also increased. The activity of glutamine synthase (GS) was unaffected by hypoglycemia. Insulin induced changes in glutamine, glutamate and their related enzymes could not be attributed to convulsion since a similar pattern of changes was observed in the preconvulsive and postconvulsive stages, and no changes were detected following picrotoxin-induced seizures.

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“…The L-isomer of 4-amino-3-isoxazolidinone (L-cycloserine) is a potent inhibitor of transaminases, especially y-aminobutyrate-transaminase (GABA-T; EC 2.6.1.19) (Severin et al, 1968;Wood et al, 1980), alanine transaminase (EC 2.6.1.2) (Profirieva and Kivman, 1967;Wong et al, 1972;Wood et al, 1978), and aspartate transaminase (EC 2.6.1.1) (Karpeisky and Breusov, 1965), and has widely been used to study the mechanisms of transamination (Karpeisky and Breusov, 1965;Churchich, 1967). Karpeisky and Breusov (1965) proposed inhibitory mechanisms of this compound on aspartate transaminase.…”

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confidence: 99%

“…The drug is therefore expected to be effective in elevating the brain GABA level and, at the same time, in lowering the concentrations of glutamate and aspartate, two putative excitatory neurotransmitters. Earlier studies have shown that intraperitoneal injection of this substance in rats delays the onset of seizures induced by strychnine, metrazol, and isonicotinic acid hydrazide (Monaco, 1958;Scotto et al, 1963;Wood et al, 1980). Correlated with this diminished susceptibility to seizures are a pronounced inhibition of GABA-T activity (Wood et al, 1978) and an increase in the GABA content of both whole brain and the synaptosomal fraction (Wood et al, 1980).…”

mentioning

confidence: 99%

“…Earlier studies have shown that intraperitoneal injection of this substance in rats delays the onset of seizures induced by strychnine, metrazol, and isonicotinic acid hydrazide (Monaco, 1958;Scotto et al, 1963;Wood et al, 1980). Correlated with this diminished susceptibility to seizures are a pronounced inhibition of GABA-T activity (Wood et al, 1978) and an increase in the GABA content of both whole brain and the synaptosomal fraction (Wood et al, 1980). Because of its reported potency in delaying the onset of chemically induced convulsions, we have tested this compound on another animal model of epilepsy, namely, sound-induced convulsion in mice, and examined in detail the changes of transmitter concentrations in the brain following administration of the drug.…”

mentioning

confidence: 99%

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L‐Cycloserine: A Potent Anticonvulsant

Chung¹,

Johnson²,

Gronenborn³

1984

Epilepsia

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The L-isomer of 4-amino-3- isoxazolidinone (L-cycloserine), a potent transaminase inhibitor, was tested for its anticonvulsant action. Intraperitoneal injection of 25 mg kg-1 protects the inbred epileptic mouse (DBA/2J) from convulsions. The drug exerts its protective influence 3 h after administration, and its effect subsides gradually thereafter. A normal mouse (CBA/Ca) can be made prone to sound-induced epilepsy by enhancing its cerebral concentrations of Zn2+ and pyridoxal-5'-phosphate (PLP). Prior administration of 25-50 mg kg-1 L-cycloserine counteracts the convulsive effects of these substances. The pretreated animal is resistant to seizures. The concentrations of glutamate and aspartate in the inferior colliculus of the treated animal are diminished, whereas the concentration of gamma-aminobutyrate is enhanced. The time course of the changes in the amino acid concentrations broadly mirrors the changes in seizure susceptibility following the treatment. Proton nuclear magnetic resonance spectra of a mixture containing equimolar concentrations of L-cycloserine, PLP, and ZnSO4 were obtained. From the resonance peaks of such an adduct, we have ascertained that a molecule of L-cycloserine forms an irreversible Schiff base with the 4-aldehyde group of PLP, and this adduct is stabilized by a zinc ion. The significance of this finding for the anticonvulsant action of the drug is discussed.

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The γ‐Aminobutyrate Content of Nerve Endings (Synaptosomes) in Mice After the Intramuscular Injection of γ‐Aminobutyrate‐Elevating Agents: A Possible Role in Anticonvulsant Activity

Cited by 63 publications

References 16 publications

Inhibition of the rate of GABA synthesis in regions of rat brain following a convulsion

Inhibition of the rate of GABA synthesis in regions of rat brain following a convulsion

Changes in the Activity of Glutamate Related Enzymes in Cerebral Cortex, During Insulin-Induced Seizures

L‐Cycloserine: A Potent Anticonvulsant

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