[H-3] NIPECOTIC ACID BINDING TO GAMMA-AMINOBUTYRIC-ACID UPTAKE SITES IN POSTMORTEM HUMAN BRAIN

Abstract: Binding of [3H]nipecotic acid, a proposed marker for GABAergic neurons, was investigated in postmortem human brain by use of a centrifugation assay. Binding was displaceable, apparently saturable, and to a single site, with typical KD and Bmax values of 1.85 μM and 124.2 pmol/mg of protein in the hippocampus. Regional distribution studies indicated a heterogeneous population of [3H]nipecotic acid binding sites with highest concentrations in the lateral globus pallidus. Putamen tissue from four cases of Huntington's disease showed a marked reduction in [3H]nipecotic acid binding. Binding correlated with both age and postmortem delay in the hippocampus. There was an effect of agonal state in which prolonged illness before death apparently caused a reduction in binding. Our results indicate that [3H]nipecotic acid may be used successfully as a marker for neuronal GABAergic uptake sites in human brain, but that the effects of variables such as age, postmortem delay, and agonal state must always be taken into account. Copyright © 1990, Wiley Blackwell. All rights reserved