Quisqualate receptors in epileptic fowl: the absence of coupling between quisqualate and N-methyl-D-aspartate receptors.
The ability of excitatory amino acid receptor agonists, AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and quisqualate to produce seizures was determined in 1-2 day old epileptic and non-epileptic (carrier) chicks. Both compounds produced prolonged clonic seizures in epileptic chicks at doses which were not convulsant in carrier chicks. Seizures produced in epileptics by AMPA were suppressed by the quisqualate antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), but were not prevented by pretreatment with competitive (2-amino-7-phosphonoheptanoic acid, APH) or non-competitive (MK-801) NMDA (N-methyl-D-aspartate) receptor antagonists. These data do not support the hypothesis that NMDA receptors work in concert with quisqualate receptors. Binding sites for [3H]AMPA were characterized in cerebral hemispheres of both epileptic and carrier chicks. Analysis of the data revealed no significant alterations in the binding affinity (KD) or the number of binding sites (Bmax) of AMPA to tissue preparations from epileptic chickens when compared to carriers. The latter data does not explain the increased susceptibility of epileptic fowl to the convulsant effects of quisqualate and AMPA.
Pedder
S C
SC
Department of Pharmacology, University of Saskatchewan, Saskatoon, Canada.
Wilcox
R I
RI
Tuchek
J M
JM
Johnson
D D
DD
Crawford
R D
RD
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002645:Chickens; D003292:Convulsants; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism*; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D010069:Oxadiazoles / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D010080:Oxazoles / Q000378:metabolism*; D016318:Quisqualic Acid; D011869:Radioligand Assay; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D000927:Anticonvulsants; D003292:Convulsants; D010069:Oxadiazoles; D010080:Oxazoles; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid