Receptors for the excitatory amino acids

1. Pharmacological evidence indicates that excitatory amino acid receptors are of three types: (a) glutamate/quisqualate-activated, GDEE-antagonized, (b) NMDA-activated, D alpha AA-antagonized, and (c) kainate-activated with no known specific antagonist. 2. Some agonists can activate both types (a) and (b); and other antagonists can affect more than one class of receptor. 3. The GDEE-sensitive receptors accept molecules in which the distal carboxyl-amino nitrogen distance approaches 0.2nm, while D alpha AA-sensitive receptors react with molecules in a more extended configuration. The "folded" receptor appears to have a higher affinity for its ligands in cases where molecules theoretically could react with either type. 4. D-glutamate can act as an agonist at the "extended" receptor and an antagonist of the "folded" type. 5. Kainate receptors appear also to be "extended" receptors perhaps physiologically activated by glutamate, but differ from those which are blocked by D alpha AA. We are grateful to Drs. J. Davies and J.C. Watkins for sending us manuscripts prior to their publication. H. McL is supported by the Medical Research Council of Canada.