On the Use of Enzyme Inhibitors to Study the Synthesis and Utilization of Brain GABA

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Abstract
Changes in the GABA concentration in different parts of the rat brain were studied following inhibition of the glutamic acid decarboxylase or the GABA-α-ketoglutaric acid aminotransferase. The GABA concentration was reduced by the decarboxylase inhibitors 4-deoxypyridoxine and isoniazid, but not by 3-mercaptopropionic acid and DL-allylglycine. The aminotransferase inhibitor γ-acetylenic GABA increased the concentration of GABA and this effect was markedly inhibited by 3-mercaptopropionic acid and partly by 4-deoxypyridoxine and isoniazid. The 4-deoxypyridoxine-induced decrease in the GABA concentration was approximately maximal after 400 mg/kg intraperitoneally and 90 min. The brain DOPA decarboxylase activity in vivo was not inhibited by 4-deoxypyridoxine. The GABA concentration in the substantia nigra was reduced by 75 per cent 4 days after section of the striato-nigral GABA neurones. In the denervated substantia nigra, 4-deoxypyridoxine did not change the concentration of GABA whereas the effect of γ-acetylenic GABA was reduced by 70 per cent.

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