USE OF [H-3] 5,7-DICHLOROKYNURENIC ACID TO IDENTIFY STRYCHNINE-INSENSITIVE GLYCINE RECEPTORS IN HUMAN POSTMORTEM BRAIN

[H-3]5,7 Dichlorokynurenic acid ([H-3]DCKA) was used to define conditi ons for obtaining selective binding to strychnine-insensitive glycine receptors. The parameters were established in sections of human brain prior to localizing the receptors sites by autoradiography. The bindin g of [H-3]DCKA was of high affinity (K-d = 14.5 nM), readily reversibl e (K_(1) = 0.216 min(-1)), and specific (60% specific binding determin ed by inhibition with 100 mu M glycine or D-serine). High levels of st rychnine-insensitive glycine receptors were identified in several brai n areas including portions of the cerebral cortex (B-max in middle tem poral gyrus: 174.0 fmol/mg tissue), basal ganglia, hippocampal formati on, and midbrain. These results identify regions where glycine recepto rs may be involved in modulating NMDA-mediated channel activity.