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Pharmacology and Regional Distribution of the Binding of 6‐[ 3 H]Nitro‐7‐Sulphamoylbenzo[ f ]‐Quinoxaline‐2,3‐Dione to Rat Brain
Author(s) -
Dev Kumlesh K.,
Petersen Vibeke,
Honoré Tage,
Henley Jeremy M.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67062609.x
Subject(s) - nbqx , ampa receptor , chemistry , unimodular matrix , kainate receptor , glutamate receptor , cnqx , ionotropic effect , pharmacology , stereochemistry , receptor , biochemistry , biology , mathematics , combinatorics
6‐Nitro‐7‐sulphamoylbenzo[ f ]quinoxaline‐2,3‐dione (NBQX) is a competitive antagonist selective for α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptors. Here we report the pharmacological characteristics and anatomical distribution of [ 3 H]NBQX binding to rat brain. The association rate of [ 3 H]NBQX to rat cerebrocortical membranes was rapid, with peak binding occurring within 10 min at 0°C. The off‐rate was also rapid, with near‐complete dissociation of the radioligand within 5 min of addition of 1 m M unlabelled l ‐glutamate. [ 3 H]NBQX bound to a single class of sites with K D and B max values of 47 n M and 2.6 pmol mg −1 of protein, respectively. The rank order of inhibition of [ 3 H]NBQX binding by AMPA receptor ligands was NBQX ≫ 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) ≥ ( S )‐5‐fluorowillardiine ≥ AMPA ≫ l ‐glutamate. The chaotrope KSCN had no effect on the IC 50 value of unlabelled NBQX displacement of [ 3 H]NBQX binding. The kainate receptor‐selective ligands NS102 and kainate were only very weak displacers. It is interesting that NBQX and CNQX displaced significantly more [ 3 H]NBQX than any of the agonists tested. Autoradiographic analysis of the binding of [ 3 H]NBQX to coronal sections showed a distribution compatible with that of [ 3 H]AMPA binding. These data indicate that [ 3 H]NBQX provides a useful novel tool to characterise the antagonist binding properties of AMPA receptors.