Zinc inhibition of t-[3H]butylbicycloorthobenzoate binding to the GABAA receptor complex.
The effect of Zn2+ on t-[3H]butylbicycloorthobenzoate ([3H]TBOB) binding to the GABAA receptor complex was studied autoradiographically in rat brain. Zn2+ inhibited [3H]TBOB binding in a dose-dependent manner at physiological concentrations. Saturation analysis revealed noncompetitive inhibition in various brain regions. The inhibitory effect of Zn2+ had regional heterogeneity; regions showing the greatest inhibition of [3H]TBOB binding were cortical laminae I-III, most areas of hippocampus, striatum, septum, and cerebellar cortex. Regions with relatively less inhibition of [3H]TBOB binding included cortical laminae V-VI, thalamus, superior colliculus, inferior colliculus, and central gray matter. The effect of Zn2+ and those of other GABAA ligands, such as benzodiazepines, bicuculline, isoguvacine, and picrotoxin, on [3H]TBOB binding seemed to be additive. Ni2+, Cd2+, and Cu2+ also inhibited [3H]TBOB binding with a regional heterogeneity similar to that produced by Zn2+. These results are consistent with Zn2+ acting at the previously detected recognition site on the GABAA receptor complex, distinct from the picrotoxin, GABA, and benzodiazepine sites. The regional heterogeneity of the Zn2+ effect may reflect differential regional distribution of GABAA receptor subtypes among brain regions. Other divalent cations probably act at the Zn2+ binding site.
Kume
A
A
Department of Neurology, University of Michigan, Ann Arbor.
Sakurai
S Y
SY
Albin
R L
RL
D000818:Animals; D001345:Autoradiography; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002413:Cations, Divalent / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism*; D014316:Tritium; D015032:Zinc / Q000494:pharmacology*
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002413:Cations, Divalent; D018079:Receptors, GABA; D014316:Tritium; C046308:tert-butylbicyclo-2-benzoate; D015032:Zinc