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  • 1
    Electronic Resource
    Electronic Resource
    Uptake of γ-Aminobutyric Acid and Glycine by Synaptosomes from Postmortem Human Brain (1986)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 47 (1986), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Synaptosomes prepared from frozen postmortem human brain accumulated the neurotransmitter γ-aminobutyric acid (GABA) and the conformationally restricted GABA analogue cis-3-aminocyclohexanecarboxylic acid (ACHC) by a sodium-dependent, temperature-sensitive, high-affinity transport process into an osmotically sensitive compartment. This transport process could be inhibited by GABA analogues (ACHC, 2,4-di-aminobutyric acid, nipecotic acid, arecaidine, guvacine) that have been shown in studies on other species to be relatively selective for neuronal rather than glial uptake systems, whereas the glial uptake inhibitor β-alanine was ineffective. Synaptosomes prepared from frozen postmortem human medulla and spinal cord, but not cerebral cortex, took up the neurotransmitter glycine by a sodium-dependent high-affinity transport process. The kinetic parameters for the high-affinity uptake of GABA, ACHC. and glycine were Km= 10 ± 3, 49 ± 19, and 35 ± 19 μM; and Vmax= 98 ± 15, 84 ± 25, and 5.5 ± 2.5 nmol/min/100 mg protein, respectively. These results demonstrate the feasibility of using human CNS preparations for studying GABA and glycine uptake, and suggest that such studies may be useful neurochemical markers for transmitter-specific presynaptic terminals in health and disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1986.tb04523.x
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  • 2
    Electronic Resource
    Electronic Resource
    Polyclonal Antibodies to the Glycine Receptor Antagonist Strychnine (1989)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 52 (1989), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Polyclonal antibodies have been raised in rabbits against the glycine receptor antagonist strychnine, coupled through a 2-amino substituent to the antigenic protein keyhole limpet haemocyanin. Strychnine binding of the predominantly immunoglobulin G (IgG) class of antibodies was measured by incubation with [3H]strychnine, followed by adsorption of IgG onto Staphylococcus aureus cells and filtration through glass-fibre filters under vacuum. Only strychnine and structurally related alkaloids or derivatives were able to inhibit [3H]strychnine binding to the IgG. A significant rank correlation was found between the potencies of these compounds to inhibit [3H]strychnine binding to the antibodies and to the glycine receptor in mouse spinal cord membranes. In contrast, preincubation of strychnine antibodies with a variety of ligands at other neurotransmitter, drug, or hormone receptors in the CNS (at 10−4M) failed to inhibit binding significantly. The failure of glycine to inhibit strychnine antibody binding is consistent with previous suggestions that the recognition sites for this amino acid on the CNS receptor may be conformationally distinct from those for the antagonist alkaloid. Strychnine antibodies may now help in the identification and purification of possible endogenous ligands at this alkaloid binding site in the CNS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1989.tb09197.x
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  • 3
    Electronic Resource
    Electronic Resource
    Uptake and Release of N-Methyl-d-Aspartate by Rat Brain Slices (1981)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 36 (1981), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The excitant amino acid, N-methyl-d-aspartate, was actively taken up by slices of rat cerebral cortex. This uptake was Na+ - and temperature-dependent, but was relatively inefficient (Km 3 MM, Vmax 0.07 μmol/g/min) compared with that of other acidic amino acids. The uptake of N-methyl-d-aspartate does not appear to have a rate-limiting influence on the time course of N-methyl-d-aspartate-induced excitation since potent uptake inhibitors, such as threo-3-hydroxy-l-aspartate, do not influence the excitant action of N-methyl-d-aspartate. The relatively prolonged excitant action of this acidic amino acid may be the result of relatively slow dissociation of the activated receptor complex. Reloaded N-methyl-d-aspartate can be released from rat brain slices by stimulation with K+ ions. Such K+-stimulated release appeared to be Ca2+-independent, unlike the K+-stimulated release of preloaded d-aspartate. These findings suggest that N-methyl-d-aspartate may be a weak but selective substrate for a glial acidic amino acid uptake system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1981.tb01676.x
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  • 4
    Electronic Resource
    Electronic Resource
    STRUCTURE-ACTIVITY STUDIES ON THE INHIBITION OF GABA BINDING TO RAT BRAIN MEMBRANES BY MUSCIMOL AND RELATED COMPOUNDS (1978)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 30 (1978), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— A series of compounds structurally related to muscimol (5-aminomethyl-3-isoxazolol) was tested as inhibitors of the sodium-independent binding of GABA to membranes from rat brain. Muscimol, 5-(l-aminoethyl)-3-isoxazolol, 5-(2-aminoethyl)-3-isoxazolol (homomuscimol), and the bicyclic derivative 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) were relatively potent inhibitors of GABA binding. THIP is an analogue of muscimol locked in a folded conformation. The structurally related compound 1,2,3,6-tetrahydropyridine-4-carboxylic acid (isoguvacine), a semirigid analogue of trans-4-aminocrotonic acid, was also a potent inhibitor of GABA binding. Apart from muscimol, these inhibitors of GABA binding did not influence the sodium-dependent,‘high-affinity’ uptake of GABA in rat brain slices, whereas the potent GABA uptake inhibitors guvacine and nipecotic acid did not influence GABA binding. The present results support previous findings that different conformational modes of GABA interact with GABA postsynaptic receptors and the neuronal GABA transport system in rat brain, and indicate that the ‘active conformation’ of GABA with respect to the receptors is partially folded and almost planar. Based on a comparison of the present results with previous in vivo studies the structural requirements for GABA-like activity in rat cerebral cortex and cat spinal cord seem to be somewhat different.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1978.tb10469.x
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  • 5
    Electronic Resource
    Electronic Resource
    ACTION OF THE NEUROTOXIN KAINIC ACID ON HIGH AFFINITY UPTAKE OF l-GLUTAMIC ACID IN RAT BRAIN SLICES (1979)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 32 (1979), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Kainic acid is a linear competitive inhibitor (Kis 250 μm) of the ‘high affinity’ uptake of l-glutamic acid into rat brain slices. Kainic acid inhibits the ‘high affinity’ uptake of l-glutamic, d-aspartic and l-aspartic acids to a similar extent. Kainic acid is not actively taken up into rat brain slices and is thus not a substrate for the ‘high affinity’ acidic amino acid transport system or any other transport system in rat brain slices. Kainic acid (300 μm) does not influence the steady-state release or potassium-stimulated release of preloaded d-aspartic acid from rat brain slices.Kainic acid binds to rat brain membranes in the absence of sodium ions in a manner indicating binding to a population of receptor sites for l-glutamic acid. Only quisqualic and l-glutamic acid inhibit kainic acid binding in a potent manner. The affinity of kainic acid for these receptor sites appears to be some 4 orders of magnitude higher than for the ‘high affinity’l-glutamic acid transport carrier.Dihydrokainic acid is approximately twice as potent as kainic acid as an inhibitor of ‘high affinity’l-glutamic acid uptake but is some 500 times less potent as an inhibitor of kainic acid binding and at least 1000 times less potent as a convulsant of immature rats on intraperitoneal injection. Dihydrokainic acid might be useful as a ‘control uptake inhibitor’ for the effects of kainic acid on ‘high affinity’l-glutamic acid uptake since it appears to have little action on excitatory receptors. N-Methyl-d-aspartic acid is a potent convulsant of immature rats, but does not inhibit kainic acid binding or ‘high affinity’l-glutamic acid uptake. N-Methyl-d-aspartic acid might be useful as a ‘control excitant’ that activates different excitatory receptors to kainic acid and does not influence ‘high affinity’l-glutamic acid uptake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1979.tb04518.x
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  • 6
    Electronic Resource
    Electronic Resource
    INHIBITION OF GABA UPTAKE IN RAT BRAIN SLICES BY NIPECOTIC ACID, VARIOUS ISOXAZOLES AND RELATED COMPOUNDS (1975)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 25 (1975), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: —A variety of isoxazoles structurally related to muscimol (3-hydroxy-5-aminomethylisoxazole) were tested as inhibitors of the uptake of GABA and some other amino acids in rat brain slices, and of the activity of the GABA-metabolizing enzymes l-glutamate 1-carboxylyase and GABA:2-oxo-glutarate aminotransferase. A bicyclic derivative, 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol, proved to be a more potent inhibitor of GABA uptake than muscimol. Structure-activity studies on this derivative, which appeared to be a competitive inhibitor of GABA uptake, led to the findings that nipecotic acid (piperidine-3-carboxylic acid) is a powerful non-competitive inhibitor of GABA uptake, and that perhydro-1,2-oxazine-6-carboxylic acid is a relatively weak competitive inhibitor of GABA uptake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1975.tb04410.x
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  • 7
    Electronic Resource
    Electronic Resource
    POSTNATAL CHANGES IN THE POTASSIUM-STIMULATED, CALCIUM-DEPENDENT RELEASE OF RADIOACTIVE GABA AND GLYCINE FROM SLICES OF RAT CENTRAL NERVOUS TISSUE (1975)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 25 (1975), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: —Using a simple apparatus designed to perfuse nervous tissue mini-slices retained on glass fibre filter discs, slices of adult (13 week) rat cerebral cortex and spinal cord were shown to release radioactive GABA and glycine, but not 2-amino-isobutyric acid, in response to increased potassium ion concentration of the perfusing medium. A major portion of this potassium-stimulated release was dependent upon the presence of calcium ions in the perfusing medium. Slices of cerebral cortex and spinal cord from rats of 1 day and 10 days postnatal age showed potassium-stimulated, calcium-dependent release of radioactive GABA and glycine respectively. These findings are consistent with other evidence that GABA and glycine are functioning as inhibitory transmitters in rats at least as soon as 1 day after birth.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1975.tb04333.x
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  • 8
    Electronic Resource
    Electronic Resource
    UPTAKE AND RELEASE OF D- AND L-ASPARTATE BY RAT BRAIN SLICES (1976)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 26 (1976), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: D-Aspartate is accumulated by slices of adult rat cortex by a high affinity uptake which is abolished if the sodium ions in the incubation medium are replaced by choline. A small uptake of D-aspartate takes place if the sodium ions are replaced by lithium ions. It appears likely that D-aspartate shares the same transport system with L-aspartate, and that the uptake of D-aspartate is into the same osmotically-sensitive particles as those which accumulate L-aspartate. D-Aspartate is released from cerebral cortex slices by raised potassium concentrations, provided calcium is present in the perfusing buffer.Both D- and L-aspartate produce gross hyperactivity when injected intraperitoneally into immature rats.Radioactive D-aspartate may be very useful in examining the neurotransmitter role of the naturally- occurring L-aspartate e.g. in studies of the autoradiographic localization of high affinity L-aspartate accumulation, its main advantage being that, unlike L-aspartate, D-aspartate does not undergo rapid metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1976.tb06485.x
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  • 9
    Electronic Resource
    Electronic Resource
    Central action of bicuculline (1974)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 23 (1974), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1974.tb06066.x
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  • 10
    Electronic Resource
    Electronic Resource
    POSTNATAL CHANGES IN THE HIGH AFFINITY UPTAKE OF GLYCINE and GABA IN THE RAT CENTRAL NERVOUS SYSTEM (1974)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 22 (1974), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— High affinity uptake systems for GABA into slices of cerebral cortex and for glycine into slices of spinal cord have been demonstrated in rats of 1 and 10 days postnatal age and compared with the systems in tissue slices from adult rats. For both systems there was an increase in the maximal rate of uptake of the substrate with development. For glycine uptake there was no significant change in apparent Km during development, whereas there was a four-fold increase in the apparent Km for GABA uptake. There were some changes with development in the apparent substrate specificity of the two systems suggesting increased specificity with maturation. Bicuculline and strychnine, antagonists of the postsynaptic inhibitory actions of GABA and glycine, produced convulsions in 1-, 2- and 10-day-old rats following intraperitoneal injection of doses somewhat lower than those required to convulse adult rats. These findings are consistent with other evidence that glycine and GABA are functioning as inhibitory transmitters at least as soon as 1 day after birth.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1974.tb12184.x
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