Abstract
An endogenous inhibitor of GABA receptor binding was prepared from synaptic membrane of rat brain with 0.05% Triton X-100. The endogenous inhibitor was competitive with GABA for GABA binding sites. The inhibition of GABA receptor binding by the endogenous inhibitor was blocked by the allosteric effect of diazepam. In the presence of diazepam, specific [3H]GABA binding was greater in a medium containing the endogenous inhibitor than in one containing an equal inhibitory potency of GABA, whereas there was no difference in the absence of diazepam. This indicated that the endogenous inhibitor was not GABA itself.
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References
Enna, S. J., andSnyder, S. H. 1977. Influence of ions, enzymes and detergents on γ-aminobutyric acid receptor binding in synaptic membranes of rat brain. Mol. Pharmacol. 13:442–453.
Enna, S. J., andSnyder, S. H. 1975. Properties of γ-aminobutyric acid (GABA) receptor binding in rat brain synaptic membrane fractions. Brain Research 100:81–97.
Zukin, S. R., Young, A. B., andSnyder, S. H. 1974. Gamma-aminobutyric acid binding to receptor sites in the rat central nervous system. Proc. Natl. Acad. Sci. U.S.A. 71:4802–4807.
Greenlee, D. V., Van Ness, P. C., andOlsen, R. W. 1978. Endogenous inhibitor of GABA binding in mammalian brain. Life Sci. 22:1653–1662.
Guidotti, A., Toffano, G., andCosta, E. 1978. An endogenous protein modulates the affinity of GABA and benzodiazepine receptors in rat brain. Nature (Lond.) 275:553–555.
Toffano, G., Guidotti, A., andCosta, E. 1978. Purification of and endogenous protein inhibitor of the high affinity binding of γ-aminobutyric acid to synaptic membranes of rat brain. Proc. Natl. Acad. Sci. U.S.A. 75:4024–4028.
Gardner, C. R., Klein, J., andGrove, J. 1981. Endogenous GABA determines the characteristics of [3H]GABA binding. European J. Pharmacol. 75:83–92.
Napias, C., Bergman, M. O., Van Ness, P. C., Greenlee, D. V., andOlsen, R. W. 1980. GABA binding in mammlian brain: Inhibition by endogenous GABA. Life Sci. 27:1001–1011.
Kuroda, H., Ogawa, N., Yamawaki, Y., Nukina, I., Ofuji, T., Yamamoto, M., andOtsuki, S. 1982. Cerebrospinal fluid GABA levels in various neurological and psychiatric diseases. J. Neurol. Neurosurg. and Psychiatry 45:257–260.
De Robertis, E., Pellegrino De Iraldi, A., Rodriguez, De Lores G., andSalganicoff, L. 1962. Cholinergic and noncholinergic nerve endings in rat brain-I. Isolation and subcellular distribution of acetylcholine and acetylcholinesterase. J. Neurochem. 9:23–25.
Marquardt, D. W. 1963. An algorithm for least-squares estimation of nonlinear parameters. J. Soc. Indust. Appl. Math. 11:431–441.
Yoneda, Y., andKuriyama, K. 1980. Presence of a low molecular weight endogenous inhibitor on [3H]muscimol binding in synaptic membranes. Nature (Lond.) 285:670–673.
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Kuroda, H., Ogawa, N., Nukina, I. et al. An endogenous inhibitor of GABA receptor binding. Neurochem Res 9, 21–27 (1984). https://doi.org/10.1007/BF00967656
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DOI: https://doi.org/10.1007/BF00967656