Localisation and properties of AMPA-insensitive kainate sites: receptor autoradiography and gene expression in rat brain.
Kainic acid (KA)-sensitive glutamate sites have been investigated by receptor autoradiography and in situ hybridisation histochemistry (ISHH) to evaluate their relationship to specific high-affinity KA receptors identified in molecular biological studies. Autoradiography with [3H]KA in the presence of the AMPA-selective antagonist NBQX (1 microM) revealed a widespread distribution of receptors through brain, especially in neocortex, hippocampal CA3, corpus striatum and granule cell layer of cerebellum. Specific binding was insensitive to the AMPA-selective agonist, S-5-fluorowillardiine, but inhibited by kainoids in a manner suggestive of receptor heterogeneity. Expression of the KA-2 receptor subunit mRNA by ISHH was also localised in hippocampal CA3 and cerebellar granule cells, suggesting some high-affinity native KA receptors labelled by [3H]KA were likely to include the KA-2 subunit in their heteromeric assembly.
Lunn
M L
ML
Department of Pharmacology, Monash University, Victoria, Australia.
Ganakas
A M
AM
Mercer
L D
LD
Lawrence
A J
AJ
Beart
P M
PM
D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D001921:Brain / Q000033:anatomy & histology*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D011744:Pyrimidinones; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists; D018092:Kainic Acid Receptors / Q000187:drug effects* / Q000235:genetics; D014498:Uracil; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
D000409:Alanine; D018690:Excitatory Amino Acid Agonists; D011744:Pyrimidinones; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D014498:Uracil; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C002872:willardiine