Regional mapping of low-affinity kainate receptors in mouse brain using [ 3H](2 S,4 R)-4-methylglutamate autoradiography

• Published in: European journal of pharmacology 2001-11, Vol.431 (3), p.305-310
• Main Authors: Bailey, Alexis, Kelland, Eve E, Thomas, Angharrad, Biggs, James, Crawford, Duncan, Kitchen, Ian, Toms, Nick J
• Format: Article
• Language: English
• Subjects: Aminoacid receptors (glycine, glutamate, gaba); AMPA receptor; Animals; Autoradiography; BALB/c; Binding Sites; Biological and medical sciences; Brain - metabolism; Brain - physiology; Brain Mapping; Cell receptors; Cell structures and functions; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Fundamental and applied biological sciences. Psychology; Glutamates - analysis; Kainate receptor; Mice; Molecular and cellular biology; mouse; Radioligand binding; Receptors, Kainic Acid - analysis; Tritium; Vertebrates: nervous system and sense organs
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(01)01463-7

Recent data indicate that (2 S,4 R)-4-methylglutamate is a selective agonist for low affinity (GluR5 and GluR6) kainate receptor subunits. In the present study, we have employed [ 3H](2 S,4 R)-4-methylglutamate to examine low affinity kainate receptor distribution in mouse brain. [ 3H](2 S,4 R)-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 [ 3H](2 S,4 R)-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)-α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) (>50 μM). [ 3H](2 S,4 R)-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 [ 3H](2 S,4 R)-4-methylglutamate is a useful radioligand for selectively labelling low affinity kainate receptors.