Zinc Inhibition of t-[3H]Butylbicycloorthobenzoate Binding to the GABAA Receptor Complex |
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Authors: | Akito Kume Sharin Y Sakurai Roger L Albin |
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Institution: | Department of Neurology, University of Michigan, Ann Arbor, Michigan, U.S.A. |
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Abstract: | Abstract: 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. |
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Keywords: | Zinc t-Butylbicycloorthobenzoate GABA GABAA receptor complex Autoradiography |
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