title: CNQX binding to non-NMDA glutamate receptors in canine cerebro-cortical crude synaptosomal membranes: pharmacological characterization and comparison of binding parameters in dogs with congenital portosystemic encephalopathy and control dogs.
abstract: The pharmacological profile and binding characteristics of the non-NMDA antagonist of glutamate receptors [3H]6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), were investigated in triton-washed crude synaptosomal membranes prepared from canine cerebral cortex. [3H]CNQX binding was inhibited by various glutamate agonists and antagonists, the rank order of potency being CNQX greater than alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) = quisqualate = kainate greater than glutamate. Two binding sites for [3H]CNQX were apparent when non-specific binding (NSB) was defined with unlabelled CNQX. In contrast, when NSB was defined with saturating concentrations of unlabelled AMPA and kainate, only one binding site was identified which corresponded to the high affinity site identified when CNQX was used to define NSB. No physiologically relevant differences were found in binding parameters for [3H]CNQX membranes from dogs with congenital portosystemic encephalopathy (PSE) when compared with control dogs. The affinity constant (Ki) of AMPA displacement of [3H]CNQX binding was not significantly different in PSE dogs compared with control dogs. These results suggest that the antagonist site on cortical non-NMDA receptors is not perturbed in dogs with congenital PSE.
authors.affiliation: Department of Pharmacology, University of Sydney, N.S.W., Australia.
authors.forename: J E
authors.initials: JE
authors.lastname: Maddison
authors.forename: W E
authors.initials: WE
authors.lastname: Watson
authors.forename: G A
authors.initials: GA
authors.lastname: Johnston
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006501:Hepatic Encephalopathy / Q000378:metabolism*; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D011810:Quinoxalines / Q000378:metabolism*; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
chemical_list: D011810:Quinoxalines; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid