[3H]nipecotic acid binding to gamma-aminobutyric acid uptake sites in postmortem human brain.
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 microM 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.
Czudek
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Department of Pathology, University of Nottingham Medical School, Queen's Medical Centre, England.
Reynolds
G P
GP
D000368:Aged; D000375:Aging / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002102:Cadaver; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009557:Nipecotic Acids / Q000378:metabolism*; D011180:Postmortem Changes; D011392:Proline / Q000031:analogs & derivatives*; D012964:Sodium / Q000494:pharmacology; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D009557:Nipecotic Acids; D014316:Tritium; C030278:nipecotic acid; D005680:gamma-Aminobutyric Acid; D011392:Proline; D012964:Sodium; C010983:homoproline