Non-NMDA glutamate receptor antagonist 3H-CNOX binds with equal affinity to two agonist states of quisqualate receptors.
Binding of 3H-CNQX to rat cortical membranes is saturable and reversible. Apparently, 3H-CNQX binds to a single site with KD = 39 nM. However, studies using AMPA as inhibitor revealed a biphasic inhibition of 3H-CNQX binding. The results suggest that CNQX binds with the same affinity to two different sites. The molecular target size of 3H-CNQX binding (51.8 +/- 3.4 kD) is equivalent to the size of the high affinity 3H-AMPA binding sites, but different from the high affinity 3H-kainate binding sites. A monoexponential decay curve for the high energy radiation inactivation analysis of 3H-CNQX binding indicates that the two 3H-CNQX binding sites have the same molecular weight and therefore might be two different conformations of the same receptor. The standard excitatory amino acids quisqualate, AMPA and kainate have a different rank order of potency as binding inhibitors at the two conformations of the quisqualate receptor.
Honore
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T
Ferrosan Research Division, Soeborg, Denmark.
Drejeŕ
J
J
Nielsen
E O
EO
Nielsen
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M
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001665:Binding Sites; D002540:Cerebral Cortex / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D008970:Molecular Weight; D010069:Oxadiazoles / Q000378:metabolism*; D011487:Protein Conformation; D011810:Quinoxalines / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013696:Temperature; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D005971:Glutamates; D007051:Ibotenic Acid; D010069:Oxadiazoles; D011810:Quinoxalines; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid