—The activities of GABA enzymes in rat cerebral cortex were studied after the administration of the convulsant, 3‐mercaptopropionic acid (MP). We found that MP markedly inhibited glutamate decarboxylase (EC 4.1.1.15) and activated GABA‐aminotransferase (EC 2.6.1.c). The level of GABA appeared to be decreased during convulsions but thereafter returned to normal. The study of the subcellular distribution of GABA enzymes after the administration of MP indicated that the glutamate decarboxylase present in the nerve endings was not affected, while GABA aminotransferase in the mitochondria was activated to a similar extent to that observed in the original homogenate. These results together with the recovery of glutamate decarboxylase activity in cortical homogenates by dialysis suggested a reversible type of inhibition, whereas the effect on GABA‐aminotransferase seemed to be more permanent.

Abstract— The effect of the convulsant, 3‐mercaptopropionic acid (MP) on the content of free amino acids and on the activity of some enzymes related to their metabolism was studied in the rat cerebellum. A decrease in the activity of glutamate decarboxylase (EC 4.1.1.15) and in the level of GABA was found; at the same time, the activity of GABA‐aminotransferase (EC 2.6.1.19) was increased. These changes coincided with a profound alteration of the morphology of the Purkinje cells which was related to the dose of MP. These findings, plus some changes in the content of other free amino acids and the activities of related enzymes, suggest that 3‐mercaptopropionic acid induces in the cerebellum an imbalance among the amino acids involved in the excitation‐inhibition mechanisms.

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Structural and biochemical alterations produced by the convulsant drug 2-amine-4-pentenoic acid (allylglycine) in the cerebellar cortex are described. Most Purkinje cells show considerable shrinkage, condensation and darkening of the cytoplasm and nucleus and the basket synapses appear swollen and with loss of synaptic vesicles. This contrasts with the normal aspect of granular cells and glomerular synapses. In the cerebellum of the convulsant rat there is 32-35% inhibition of glutamic acid decarboxylase. Kinetic studies suggest that the inhibition is due to a competitive inhibition for the substrate. These results suggest that allylglycine may be used as a tool for the study in the central nervous system of inhibitory systems mediated by y-aminobutyric acid. Int J Neurosci Downloaded from informahealthcare.com by University of Newcastle on 12/26/14 For personal use only. PhQTWCOZOg~ 12: 989-1.000. Int J Neurosci Downloaded from informahealthcare.com by University of Newcastle on 12/26/14 For personal use only.