Abstract
Synaptosomes and synaptoneurosomes were prepared from the cerebral cortex of control rats and of rats treated with gabaculine, gamma-vinylGABA (GVG), hydrazine and isonicotinic acid hydrazide (INH). An inverse relationship was observed between the GABA content of the synaptoneurosomes and the muscimol-stimulated chloride ion uptake by the organelles. The relationship held over an extensive range of experimental conditions including different drugs, different dosage levels of the same drug, different time intervals after administration of the same drug, and both single and multiple injections of drugs. The results indicated that the phenomenon was associated with the neurosome component of the preparation, and raised the possibility that GABA levels within the postsynaptic cell might regulate the functioning of the GABAA receptor complex
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Wood J. D., and Davies, M., 1989. Regulation of the γ-aminobutyric acidA receptor by γ-aminobutyric acid levels within the postsynaptic cell. J. Neurochem. 53:1648–1651.
Rando, R. R. and Bangerter, F. W. 1977. The in vivo inhibition of GABA-transaminase by gabaculine. Biochem Biophys. Res. Comm. 76:1276–1281.
Jung, M. J., Lippert, B., Metcalf, B. W., Bohlen, P., and Schechter, P. J. 1977. Gamma-vinyl GABA (4-amino-hex-5-enoic acid), a new selective inhibitor of GABA-T: effects on brain GABA metabolism in mice. J. Neurochem. 29:797–802.
Balzer, H., Holtz, P., and Palm, D. 1960. On the mechanism of the convulsant effect of hydrazides in mice. Biochem. Pharmacol. 5:169–171.
Wood, J. D., and Russell, M. P. 1980. 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. J. Neurochem. 35:125–130.
Wood, J. D., Russell, M. P., Kurylo, E., and Newstead, J. D. 1979. Stability of synaptosomal GABA levels and their use in determining the in vivo effects of drugs: convulsant agents. J. Neurochem. 33:61–68.
Cotman, C. W. 1974. Isolation of synaptosomal and synaptic plasma membrane fractions. Methods in Enzymology 31:445–452.
Schwartz, R. D., Jackson, J. A., Weigert, D., Skolnick, P., and Paul, S. M. 1985. Characterization of barbiturate-stimulated chloride efflux from rat brain synaptoneurosomes. J. Neurosci. 5:2963–2970.
Schwartz, R. D., Suzdak, P. D., and Paul, S. M. 1986. γ-Aminobutyric acid (GABA) and barbiturate mediated36Cl-uptake in rat brain synaptoneurosomes: evidence for rapid desensitization of the GABA receptor-coupled chloride ion channel. Mol. Pharmacol. 30:419–426.
Lenda, K., and Svenneby, G. 1980. Rapid high performance liquid chromatographic determination of amino acids in synaptosomal extracts. J. Chromatog. 198:516–519.
Geddes, J. W., and Wood, J. D. 1984. Changes in the amino acid content of nerve endings (synaptosomes) induced by drugs that alter the metabolism of glutamate and γ-aminobutyric acid. J. Neurochem. 42:16–24.
Hartree, E. F. 1972. Determination of protein: a modification of the Lowry method that gives a linear photometric response. Anal. Biochem. 48:422–427.
Macvicar, B. A., Tse, F. W. Y., Crichton, S. A., and Kettenmann, H. 1989. GABA-activated Cl- channels in astrocytes of hippocampal slices. J. Neurosci. 9:3577–3583.
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Special issue dedicated to Dr. Eugene Roberts.
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Wood, J.D., Davies, M. Regulation of the GABAA receptor/ion channel complex by intracellular GABA levels. Neurochem Res 16, 375–379 (1991). https://doi.org/10.1007/BF00966101
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DOI: https://doi.org/10.1007/BF00966101