Autoradiographic characterization of N-methyl-D-aspartate-, quisqualate- and kainate-sensitive glutamate binding sites.
Quantitative autoradiography was used to characterize the pharmacological specificity and anatomical distributions of subtypes of L-[3H]glutamate binding sites in rat brain. One population of sites was sensitive to N-methyl-D-aspartate (NMDA) and other compounds thought to be specific for the NMDA receptor. This site was enriched in stratum radiatum of hippocampus (CA1) where it constituted about 80% of glutamate binding sites and it represented a variable portion of glutamate binding sites throughout the brain. A second population of sites had a high affinity for quisqualate. Approximately 80% of glutamate binding sites in cerebellar molecular layer were of the high affinity quisqualate type. The number of these sites was greatly increased in the presence of Cl- and Ca++ ions. A subset of the high affinity quisqualate sites was sensitive to competition by kainate, particularly in stratum lucidum of hippocampus; the density of these high affinity kainate-sensitive sites was decreased in the presence of Ca++ but not Cl- ions. At high concentrations quisqualate competes for all glutamate binding sites, as reported previously. There was a good correspondence between the density and distribution of low affinity quisqualate sites and NMDA-sensitive sites. Pharmacological analysis suggested that the low affinity quisqualate site and the NMDA site are equivalent. Anatomical and pharmacological evidence suggests that the NMDA-, (high affinity) quisqualate- and kainate-sensitive glutamate binding sites may correspond to the physiologically defined NMDA, quisqualate and kainate receptors.
Greenamyre
J T
JT
Olson
J M
JM
Penney
J B
JB
Young
A B
AB
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D002118:Calcium / Q000494:pharmacology; D002531:Cerebellum / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000378:metabolism; D016318:Quisqualic Acid; D051381:Rats; D018091:Receptors, AMPA; D011955:Receptors, Drug / Q000378:metabolism*; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D001224:Aspartic Acid; D002118:Calcium; D002712:Chlorides; D005971:Glutamates; D016202:N-Methylaspartate; D010069:Oxadiazoles; D016318:Quisqualic Acid; D018091:Receptors, AMPA; D011955:Receptors, Drug; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter