Analogue interactions with the brain receptor labeled by [³H]kainic acid

The kinetics of interaction of kainic acid analogues and reputed antagonists of acidic excitatory amino acids with a specific binding site for [³H]α-kainic acid were examined in washed cerebellar membranes incubated at 4°C. The avidity of both l-glutamate (1.5 μM) and quisqualate (0.6 μM) suggests that proper orientation of the two carboxyls in the amino group is essential for binding to one component of the receptor. The high affinity of domoate, α-kainate and α-keto-kainate as compared to the low affinity of dihydrokainate and α-allo-kainate indicate that a pi electron group with appropriate cis-planar orientation versus the C2-carboxyl group is essential for high affinity binding to the receptor. These studies provide additional evidence that the recognition site labeled by [³H]kainic acid represents the receptor mediating its neurophysiologic and neurotoxic effects.