[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.
Sundman
I
I
Department of Psychiatry, University of Umeå, Sweden.
Lernmark
U
U
Marcusson
J
J
D000368:Aged; D001344:Autopsy; D001667:Binding, Competitive / Q000502:physiology; D015415:Biomarkers / Q000737:chemistry; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism*; D009557:Nipecotic Acids / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives*; D011963:Receptors, GABA-A / Q000378:metabolism*; D013696:Temperature; D014316:Tritium
D015415:Biomarkers; D009557:Nipecotic Acids; D011963:Receptors, GABA-A; D014316:Tritium; C030278:nipecotic acid; D011392:Proline; C010983:homoproline