Isolation and characterization of endogenous modulators for GABA system |
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Authors: | M. Yarom J. Bao X. -W. Tang E. Wu Y. H. Lee W. H. Tsai J. -Y. Wu |
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Affiliation: | (1) Department of Physiology and Cell Biology, Division of Biological Sciences, University of Kansas, 3027 Haworth Hall, 66045 Lawrence, KS;(2) Institute of Biomedical Sciences, Academia Sinica, 3027 Haworth Hall, Taipei, Taiwan ROC |
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Abstract: | Pig brain extracts from both soluble and membrane fractions were found to contain potent inhibitors for GABA synthesizing enzyme, GAD, referred to as endogenous GAD inhibitors (EGIs) and for the binding of GABA agonist, muscimol, referred to as muscimol binding inhibitors (MBIs). EGIs and MBIs were first purified through gel-filtration Bio-Gel P-2 columns, in which multiple activity peaks were observed. One of them appears to be co-eluted with eitherl-glutamate or GABA. However, others are clearly separated froml-glutamate or GABA. EGIs were found to be low MW (<1,800 dalton), heat and acid-base stable, negatively charged, non hydrophobic substances. MBIs were found to be low MW (<1,800 dalton) neutral or positively charged substances. MBIs had no effect on [3H]flunitrazepam (FNZP) binding, indicating that they are not endogenous benzodiazepine receptor ligands and they may act specifically on GABA binding site.Special issue dedicated to Dr. Frederick E. Samson |
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Keywords: | Endogenous inhibitors glutamate decarboxylase GABAA receptor GABA |
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