On the use of enzyme inhibitors to study the synthesis and utilization of brain GABA

Changes in the GABA concentration in different parts of the rat brain were studied following inhibition of the glutamic acid decarboxylase or the GABA-alpha-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 gamma-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 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 gamma-acetylenic GABA was reduced by 70 per cent.