EFFECTS OF L-TRANS-PYRROLIDINE-2,4-DICARBOXYLATE AND L-THREO-3-HYDROXYASPARTATE ON THE BINDING OF [H-3] L-ASPARTATE, [H-3] ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONATE (AMPA), [H-3] DL-(E)-2-AMINO-4-PROPYL-5-PHOSPHONO-3-PENTENOATE (CGP-39653), [H-3] 6-CYANO-7-NITROQUINOXALINE-2,3-DIONE (CNQX) AND [H-3] KAINATE STUDIED BY AUTORADIOGRAPHY IN RAT FOREBRAIN

L-trans-Pyrrolidine-2,4-dicarboxylate (L-t-PDC) and L-threo-3-hydroxy aspartate (L-t-30HA), compounds known to interact strongly with the Na+-dependent high affinity uptake of excitatory amino acids in central nervous tissue, were tested as potential inhibitors of binding to glutamate receptors and transport sites in frozen sections of rat brain. [H-3]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), [H-3]6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). and [H-3]kainate were used as ligands for the binding sites on the ''non-NMDA' classes of glutamate receptors and [H-3]DL-(E)-2-amino-4-propyl-5-phosphono-3-pentenoate (CGP 39653) was used to label NMDA receptor binding sites. The Na+-dependent glutamate-uptake site was marked by [H-3]L-aspartate. The autoradiograms, obtained by exposing H-3-sensitive film to sections of rat forebrain preincubated with H-3-labelled ligands, were scanned by laser beam and quantified. Distribution patterns of the receptor and transporter sites visualized by the H-3-labelled ligands were compatible with previously published results. [H-3]CNQX binding, however, was found to be significantly decreased by Na+. L-t-30HA was about an order of magnitude stronger than L-t-PDC as an inhibitor of [H-3]L-aspartate binding. Neither of the compounds had any important effect at the ''non-NMDA'' receptor binding sites but L-t-30HA was a weak inhibitor of [H-3]CGP 39653 binding (<40% at 100 mu M). The results suggest that, at low nanomolar concentrations, both compounds are likely to be selective for Na+-dependent high affinity glutamate transporter sites. Moreover, L-t-30HA seems to have a sufficiently high affinity for the site to be almost certainly useful, if available in a H-3-labelled form; as a ligand in autoradiographic studies.