Abstract
Synaptosomes isolated from mouse brain were incubated with [14C]glutamate and [3H]γ-aminobutyric acid ([3H]GABA), and then [14C]GABA (newly synthesized GABA) and [3H]GABA (newly captured GABA) in the synaptosomes were analysed. (1) the [3H]GABA was rapidly degraded in the synaptosomes, (2) when the synaptosomes were treated with gabaculine (a potent inhibitor of GABA aminotransferase), the degradation of [3H]GABA was strongly inhibited, (3) the gabaculine treatment brough about a significant increase in Ca2+-independent release of [3H]GABA with no effect on Ca2+-dependent release, (4) no effects of gabaculine on degradation and release of [14C]GABA were observed. The results indicate that there are at least two pools of GABA in synaptosomes and support the possibilities that GABA taken up into a pool which is under the influence of GABA aminotransferase is released Ca2+-independently and that GABA synthesized in another pool which is not under the influence of GABA aminotransferase is released Ca2+-dependently.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Hoshino, M., Asakura, T., and Matsuda, M. 1979. Release of γ-aminobutyric acid from isolated brain synaptosomes during semicarbazide-induced convulsions. J. Nutri. Sci. Vitaminol. 25:367–374.
Wood, J. D., Kurylo, E., and Lane, R. 1988. γ-Aminobutyric acid release from synaptosomes prepared from rats treated with isonicotinic acid hydrazide and gabaculine. J. Neurochem. 50:1839–1843.
Abe, M., and Matsuda, M. 1983. On the existence of two GABA pools associated with newly synthesized GABA and with newly taken up GABA in nerve terminals. Neurochem. Res. 8:563–572.
Gray, E. G., and Whittaker, V. P. 1962. The isolation of nerve endings from brain: An electron-microscopic study of cell fragments derived by homogenization and centrifugation. J. Anat. 96:79–88.
Sellström, Å., Sjöberg, L.-B., and Hamberger, A. 1975. Neuronal and glial systems for γ-aminobutyric acid metabolism. J. Neurochem. 25:393–398.
Sakurai, T., Abe, M., and Matsuda, M. 1981. The effects of administration of semicarbazide and aminooxyacetic acid on B6 vitamer levels in subcellular fractions of mouse brain. J. Nutri. Sci. Vitaminol. 27:529–538.
Chude, O., and Wu, J.-Y. 1976. A rapid method for assaying enzymes whose substrates and products differ by charge. Application to brainl-glutamate decarboxylase. J. Neurochem. 27:83–86.
Hall, Z. W., and Kravitz, E. A. 1967. The metabolism of γ-amiobutyric acid (GABA) in the lobster nervous system-I. GABA-glutamate transaminase. J. Neurochem. 14:45–54.
Raiteri, M., Federico, R., Coletti, A., and Levi, G. 1974. Release and exchange studies relating to the synaptosomal uptake of GABA. Eur. J. Pharmacol. 25:411–414.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with the Foline phenol reagent. J. Biol. Chem. 193:265–275.
Rando, R. R. 1977. Mechanism of the irreversible inhibition of γ-aminobutyric acid-α-ketoglutaric acid transaminase by the neurotoxin gabaculine. Biochemistry 16:4604–4610.
Rando, R. R., and Bangerter, F. W. 1977. The in vivo inhibition of GABA-transaminase by gabaculine. Biochem. Biophys. Res. Commun. 76:1276–1281.
Gram, L., Larsson, O. M., Johnsen, A. H., and Schousboe, A. 1988. Effects of valproate, vigabatrin and aminooxyacetic acid on release of endogenous and exogenous GABA from cultured neurons. Epilepsy Res. 2:87–95.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Asakura, T., Matsuda, M. Effect of gabaculine on metabolism and release of γ-aminobutyric acid in synaptosomes. Neurochem Res 15, 295–300 (1990). https://doi.org/10.1007/BF00968675
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00968675