[3H]nipecotic acid binding to GABA uptake sites in human brain

The binding of [3H]nipecotic acid to frozen post-mortem human brain tissue has been characterized. Competition experiments with gamma-aminobutyric acid (GABA), GABA uptake inhibitors, ligands active at post-synaptic GABA receptors and receptors for other neurotransmitter systems, suggest that [3H]nipecotic acid binds to the neuronal (but not glial) GABA uptake site. Competition and kinetic experiments suggest that 85% of the binding is to a high affinity site. The dissociation constants (Kd) measured in kinetic and equilibrium experiments were in the same range (0.5-0.6 microM). The regional distribution was studied in 19 brain regions and the binding was relatively homogenous. It is concluded that [3H]nipecotic acid binding can be used as a marker for neuronal GABA uptake sites in post-mortem human brain tissue.