INHIBITION OF EXCITATORY AMINO ACID-STIMULATED PHOSPHOINOSITIDE HYDROLYSIS IN RAT HIPPOCAMPUS BY L-ASPARTATE-BETA-HYDROXAMATE

The effect of a series of glutamate uptake inhibitors was tested on ibotenate-stimulated phosphoinositide hydrolysis. The pharmacological profile of the inhibitory effect of these compounds on the ibotenate response was quite different from that on glutamate uptake. Aspartate-beta-hydroxamate was the most potent compound with the L-isomer (IC50 11 +/- 2-mu-M) being considerably more potent than the D-isomer (IC50 104 +/- 12-mu-M). The effect of the L-aspartate-beta-hydroxamate was found to be specific for ibotenate and quisqualate-stimulated phosphoinositide hydrolysis; this compound did not affect hydrolysis stimulated by carbachol, K+ or sodium fluoride. The inhibition of the ibotenate response was found to involve a non-competitive and irreversible mechanism.