Use of [3H]5,7 dichlorokynurenic acid to identify strychnine-insensitive glycine receptors in human postmortem brain.
[3H]5,7 Dichlorokynurenic acid ([3H]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 [3H]DCKA was of high affinity (Kd = 14.5 nM), readily reversible (K-1 = 0.216 min-1), and specific (60% specific binding determined by inhibition with 100 microM glycine or D-serine). High levels of strychnine-insensitive glycine receptors were identified in several brain areas including portions of the cerebral cortex (Bmax 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.
Wamsley
J K
JK
Department of Psychiatry, New York Medical College, Valhalla 10595.
Sofia
R D
RD
Faull
R L
RL
Ary
T
T
Narang
N
N
McCabe
R T
RT
D001345:Autoradiography; D001479:Basal Ganglia / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D008636:Mesencephalon / Q000187:drug effects; D011869:Radioligand Assay; D018009:Receptors, Glycine / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013331:Strychnine / Q000494:pharmacology; D014316:Tritium
D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D007736:Kynurenic Acid; D013331:Strychnine; C066192:5,7-dichlorokynurenic acid