Binding of the cage convulsant, [3H]TBOB, to sites linked to the GABAA receptor complex.
[3H]t-Butylbicycloorthobenzoate ([3H]TBOB) binds to specific sites on crude synaptic rat brain membranes. The dissociation constant, Kd, determined from saturation experiments is near 8 nM and the receptor density Bmax is about 20 pmol/g wet tissue. Non-specific binding constitutes about 35% of the total binding at 4 nM [3H]TBOB. The association of [3H]TBOB is monophasic but its dissociation is biphasic. Kd values of 8 nM (70% of the binding sites) and 20 nM (30% of the binding sites) were estimated from the kinetic data. These values differ from those previously reported. Specifically bound [3H]TBOB is displaced by picrotoxin and by t-butylbicyclophosphorothionate (TBPS). No simple competitive interaction of picrotoxin with [3H]TBOB binding was found. Micromolar quantities of the GABAergic facilitating compounds, GABA, muscimol and diazepam inhibited [3H]TBOB binding in an allosteric manner.
Van Rijn
C M
CM
Department of Comparative and Physiological Psychology, University of Nijmegen, The Netherlands.
Willems-van Bree
E
E
Van der Velden
T J
TJ
Rodrigues de Miranda
J F
JF
D000818:Animals; D001667:Binding, Competitive; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D010852:Picrotoxin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D010852:Picrotoxin; D011963:Receptors, GABA-A; C046308:tert-butylbicyclo-2-benzoate