GLUTAMIC ACID DECARBOXYLASE INHIBITION AND ULTRASTRUCTURAL CHANGES BY CONVULSANT DRUG ALLYLGLYCINE

The effects in vivo and vitro of the convulsant drug allylglycine on the activity of glutamic acid decarboxylase (GAD), aminobutyrate aminotransferase, glutamine synthetase and aspartate- and alanine-aminotransferases of the rat cerebral cortex were studied. The most significant result was the finding of an inhibition of GAD, during the period of convulsion, which was even greater by addition in vitro of the drug. This inhibition is not by way of the cofactor, pyridoxal phosphate. Preincubation of the homogenate with allylglycine enhanced the inhibition, while preincubation in buffer-substrate produced a protective effect. The inhibition of GAD was correlated with a decrease of 40 per cent in the concentration of γ-aminobutyric acid in the cerebral cortex. In the convulsant rat, ultra-structural alterations of some nerve endings of the cerebral cortex were observed. After cell fractionation, such altered nerve endings were preferentially found in the GAD-rich (nonaminergic) fraction of isolated nerve endings. The possible mechanism of the convulsions induced by allyglycine is discussed and a specific effect on GAD-rich inhibitory nerve endings is postulated. © 1969.