Quantitative autoradiography of 4'-ethynyl-4-n-[2,3-3H2]propylbicycloorthobenzoate binding to the GABAA receptor complex.
4'-Ethynyl-4-n-[2,3-3H2]propylbicycloorthobenzoate ([3H]EBOB) binding to the GABAA receptor complex was characterized autoradiographically in rat brain and then its binding in human brain was investigated. [3H]EBOB binding was saturable, specific and identified a single population of binding sites. The Kd obtained from saturation studies was 4.59 nM. Picrotoxin produced dose-dependent inhibition of [3H]EBOB binding and saturation analysis indicated a competitive interaction. Isoguvacine inhibited [3H]EBOB binding with regionally different effects. Bicuculline increased [3H]EBOB binding only in the cerebellar granule cell layer. In human cerebellum, a high level of [3H]EBOB binding sites was seen in the granule cell layer. These results suggest that [3H]EBOB binds to the picrotoxin binding site associated with the GABAA receptor complex, that regional differences in GABAA agonist and antagonist modulation of [3H]EBOB binding reflect underlying regional differences in GABAA receptor subunit composition, and that there is a species difference in GABAA receptor distribution between human and rat cerebellum.
Kume
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Department of Neurology, University of Michigan, Ann Arbor 48104.
Albin
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001345:Autoradiography; D001640:Bicuculline; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018755:GABA Agonists / Q000494:pharmacology; D006801:Humans; D007539:Isonicotinic Acids / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism*; D013045:Species Specificity
D001640:Bicuculline; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018755:GABA Agonists; D007539:Isonicotinic Acids; D010852:Picrotoxin; D018079:Receptors, GABA; C091518:1-(4-ethynylphenyl)-4-propyl-2,6,7-trioxabicyclo(2.2.2)octane; C015300:isoguvacine