INHIBITION OF THE GLUTAMATE TRANSPORTER AND GLIAL ENZYMES IN RAT STRIATUM BY THE GLIOTOXIN, ALPHA-AMINOADIPATE

1 The effect of the gliotoxic analogue of glutamate, alpha aminoadipat e, on the high affinity transport of D-[H-3]-aspartate into a crude st riatal P-2 preparation, and on the activity of two enzymes of which gl utamate is the substrate has been examined. 2 The L-isomer of alpha am inoadipate competitively inhibited the transport protein, with a K-i v alue of 192 mu M, whereas the D-isomer of alpha aminoadipate was ineff ective. The potent convulsant, L-methionine-S-sulphoximine, was also w ithout effect on the activity of the gluatmate transport protein. 3 L- alpha Aminoadipate was a competitive inhibitor of both glutamine synth etase, and gamma-glutamylcysteine synthetase, with K-i values of 209 m u M and 7 mM respectively. Once again, the D-isomer of alpha aminoadip ate was a far weaker inhibitor of either enzyme. 4 The results are dis cussed in terms of the mechanism of action of alpha aminoadipate in ca using toxicity of glial cells.