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Regional mapping of low-affinity kainate receptors in mouse brain using [(3)H](2S,4R)-4-methylglutamate
A Bailey1, E E Kelland, A Thomas
1School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK.
Abstract:
Recent data indicate that (2S,4R)-4-methylglutamate is a selective agonist for low affinity (GluR5 and GluR6) kainate receptor subunits. In the present study, we have employed [(3)H](2S,4R)-4-methylglutamate to examine low affinity kainate receptor distribution in mouse brain. [(3)H](2S,4R)-4-Methylglutamate labelled a single site in murine cerebrocortical membranes (K(d)=9.9+/-2.7 nM, B(max)=296.3+/-27.1 fmol mg protein(-1)). The binding of 8 nM [(3)H](2S,4R)-4-methylglutamate was displaced by several non-NMDA receptor ligands (K(i)+/-S.E.M.): domoate (1.1+/-0.2 nM)>kainate (7.1+/-1.1 nM) >> L-glutamate (187.6+/-31.9 nM) >> (S)-alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) (>50 microM). [(3)H](2S,4R)-4-Methylglutamate autoradiography revealed a widespread regional distribution of low affinity kainate receptors. Highest binding densities occurred within deep layers of the cerebral cortex, olfactory bulb, basolateral amygdala and hippocampal CA3 subregion. Moderate labelling was also evident in the nucleus accumbens, dentate gyrus, caudate putamen, hypothalamus and cerebellar granule cell layer. These data show that [(3)H](2S,4R)-4-methylglutamate is a useful radioligand for selectively labelling low affinity kainate receptors.
