Use of [3H]5,7 dichlorokynurenic acid to identify strychnine-insensitive glycine receptors in human postmortem brain

Abstract [ 3 H]5,7 Dichlorokynurenic acid ([ 3 H]DCKA) was used to define conditions 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 binding of [ 3 H]DCKA was of high affinity ( K d = 14.5 nM ), readily reversible ( K −1 = 0.216 min −1 ), and specific (60% specific binding determined by inhibition with 100 μM glycine or d -serine). High levels of strychnine-insensitive glycine receptors were identified in several brain areas including portions of the cerebral cortex ( B max in middle temporal gyrus: 174.0 fmol/mg tissue), basal ganglia, hippocampal formation, and midbrain. These results identify regions where glycine receptors may be involved in modulating NMDA-mediated channel activity.