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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: A possible alternative route for production of a small glutamate pool in brain is from proline or ornithine to 1-pyrroline-5-carboxylate (P5C) and thence to glutamate. The conversion from ornithine to P5C is catalyzed by ornithine δ-aminotransferase (OrnT) whereas that from proline is catalyzed by proline oxidase (PrO). The conversion of P5C to glutamate is catalyzed by 1-pyrroline-5-carboxylate dehydrogenase (PDH). Biochemical assays of PDH and PrO in various rat brain regions indicate no positive correlation between the two enzymes nor between either activity and high-affinity glutamate uptake or the regional distribution of OrnT. We have localized PDH and PrO histochemically by modifications of the Van Gelder [J. Neurochem.12, 231–237, (1965)] method for γ-aminobutyric acid (GABA) transaminase. The enzymes were found only in certain types of glial cells; the best stained were the Bergmann glial cells of the cerebellum but, for PDH, there was also good staining of astrocytes in the dentate area of the hippocampus. Since both these areas are believed to have heavy glutamate innervation and numerous GABA interneurons, these findings may reflect an alternative route of glutamate production in glial cells near some glutamate and/or GABA tracts but they do not support this as a possible route for glutamate formation in most brain regions. The findings do, however, provide further evidence for chemical specialization of glial cells.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Injection of folic acid (FA) into the nucleus substantia innominata (NSI) was found to decrease [3H]quinuclidinyl benzilate ([3H]QNB) binding in the frontal cortex, pyriform cortex, amygdala, and the NSI itself without changing the Kd. Binding in the thalamus, caudate nucleus, hippocampus, and substantia nigra was not affected. [3H]Flunitrazepam binding was unchanged in all eight regions studied. Previous work indicates FA injections into the NSI produce epileptiform activity and cause loss of GABAergic and possibly other neurons in the frontal and pyriform cortices, the amygdala, and thalamus. The reductions of [3H]QNB binding in the first three of these regions are interpreted as indicating that many of the neurons lost are cholinoceptive, a finding that supports the previous hypothesis that activation of cholinergic projections from the NSI is an important part of the mechanism of cell loss in these regions.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 29 (1977), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 36 (1981), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: A radiometric assay for ornithine aminotransferase was developed using [1-14C]α-ketoglutarate as the labeled substrate and glutamate decarboxylation as a linking step. This assay gives near total measurement of ornithine aminotransferase activities that are, respectively, about 1.5 and 10 times larger than those obtained by the spectrophotometric assay and the radiometric assay using [1-14C]ornithine. It is also the most sensitive of the three assay procedures.Consistent with previous reports, brain ornithine aminotransferase was found to be present predominantly in synaptosomes. Regional distribution of the enzyme correlated with that of the high-affinity uptake of glutamate, but not with the distribution of glutamate decarboxylase. Ornithine aminotransferase may be responsible for the synthesis of glutamate in glutamatergic neurons but it is clearly not localized exclusively in such neurons.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 13 (1986), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. It was observed that the effectiveness of diazepam in causing sleep, as denned by the loss of righting reflex, was significantly decreased after a single exposure to either diazepam or lorazepam.2. RO 15-1788, a benzodiazepine antagonist, in contrast did not induce tolerance to diazepam. The mechanism for this acute tolerance is unclear. The rapidity in its development may exclude metabolic tolerance while alterations in brain sensitivity to diazepam remain a possibility.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 13 (1986), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The tolerance to the hypnotic effect of diazepam developed after a single exposure to diazepam in the presence or absence of cycloheximide, which blocks liver enzyme induction, was studied.2. At the high dose (30-35 mg/kg) used in this study, diazepam was found to be metabolized very rapidly in mice, consistent with previous findings using a much smaller dose (5 mg/kg).3. There was no significant difference in the pharmacokinetics of diazepam in control and tolerant mice as observed by monitoring the plasma and brain concentrations of diazepam and N-desmethyldiazepam.4. It is concluded that acute tolerance to diazepam in mice may not be attributed to changes in pharmacokinetic factors.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0533
    Keywords: Key words Excitatory amino acids ; N-Methyl-d-aspartate receptors ; Nitric oxide ; Arcuate nucleus ; Monosodium glutamate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glutamate-, aspartate-, N-methyl-d-aspartate receptor (NMDAR1 and 2 subunits)-, and nitric oxide synthase (NOS)-immunoreactive neurons were studied in the arcuate nucleus (AN) of mice treated neonatally with monosodium glutamate (MSG) which is known to cause extensive neuronal loss in this hypothalamic nucleus. It was found that intensely stained glutamate- and aspartate-immunoreactive neurons present in the AN of control mice were completely absent in the MSG-lesioned AN as well as the ventromedial nucleus lateral to the AN. Similarly, NMDAR1-immunoreactive neurons were mostly absent in the MSG-lesioned AN but remained intact in the ventromedial nucleus. There was also a substantial loss of NMDAR2 immunoreactivity within the AN. In contrast, NOS-immunoreactive neurons in the AN survived the neonatal glutamate treatment, although they appeared to be less intensely stained.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Behavior genetics 18 (1988), S. 185-191 
    ISSN: 1573-3297
    Keywords: selective breeding ; diazepam ; differential sensitivity ; heritability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract A selective breeding study for differential sensitivity to diazepam was carried out from an outbred stock of Swiss albino mice. Mice were selected and mated according to their sleep times in response to a low hypnotic dose of 35 mg/kg diazepam. Only brother/sister mating was allowed for subsequent generations. Over six generations of two-way selection, it appears that upward selection for increased sleep time to diazepam was more effective, with a realized heritability of .7, compared to .3 for downward selection. It is concluded that a mouse line has been established that exhibits a relatively long sleep duration in response to diazepam administration.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Neurochemical research 11 (1986), S. 1379-1382 
    ISSN: 1573-6903
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Phenytoin was observed to inhibit competitively the sodium dependent high affinity synaptosomal transport of both glutamate (Glu) and γ-aminobutyric acid (GABA) withK i values of 66±10 and 185±65 μM, respectively. This constrasted with a previous report that the uptakes of Glu and GABA were enhanced by phenytoin. The degree of inhibition is dependent on the concentrations of the competing drug and substrate present. Taking the therapeutic levels of phenytoin and the overall brain Glu and GABA contents, the degrees of inhibition obtainble appear to be negligible. However, as most of the high levels of Glu and GABA in the brain are intracellular, Glu, and GABA concentrations in the microenvironment of the uptake sites may be sufficiently small so that the ability of phenytoin to inhibit Glu and GABA transport may contribute significantly to the anticonvulsant property of this drug.
    Type of Medium: Electronic Resource
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