Cooperative interactions at [3H]kainic acid binding sites in rat and human cerebellum

Inhibition of the specific binding of [3H]kainic acid was studied in membranes isolated from rat and human cerebellum; the sequence of potencies in both species were: kainic acid greater than L-glutamic acid greater than dihydrokainic acid greater than D-glutamic acid. Whereas the Hill coefficient for unlabelled Kainate was 1.0, dihydrokainic acid and D- and L-glutamic acids exhibited negative cooperativity with Hill coefficients of near 0.5. This allosteric interaction of glutamic acid at the kainic acid recognition site suggests a biochemical correlate for the synergistic effects of these compounds in vivo.