Effects of increased gamma-aminobutyric acid levels on GAD67 protein and mRNA levels in rat cerebral cortex.
Rats were injected with saline or the gamma-aminobutyric acid (GABA) transaminase inhibitor gamma-vinyl-GABA for 7 days and the effects on GABA content and glutamic acid decarboxylase (GAD) activity, and the protein and mRNA levels of the two forms of GAD (GAD67 and GAD65) in the cerebral cortex were studied. gamma-Vinyl-GABA induced a 2.3-fold increase in GABA content, whereas total GAD activity decreased by 30%. Quantitative immunoblotting showed that the decline in GAD activity was attributable to a 75-80% decrease in GAD67 levels, whereas the levels of GAD65 remained unchanged. RNA slot-blotting with a 32P-labeled GAD67 cDNA probe demonstrated that the change in GAD67 protein content was not associated with a change in GAD67 mRNA levels. Our results suggest that GABA specifically controls the level of GAD67 protein. This effect may be mediated by a decreased translation of the GAD67 mRNA and/or a change in the stability of the GAD67 protein.
Rimvall
K
K
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany, NY 12201-0509.
Sheikh
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SN
Martin
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D000614:Aminocaproates / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D015152:Blotting, Northern; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D015151:Immunoblotting; D007527:Isoenzymes / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000614:Aminocaproates; D000927:Anticonvulsants; D007527:Isoenzymes; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; D020888:Vigabatrin