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

Abstract

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 car☐yls 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-car☐yl 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.