Selective association of N-methyl aspartate and quisqualate types of L-glutamate receptor with brain postsynaptic densities.
Recognition sites for the excitatory neurotransmitter, L-glutamate, were studied in synaptic plasma membranes and postsynaptic densities (PSDs) isolated from rat brains. The results demonstrate (i) that L-glutamate binding sites may be resolved into three distinct subtypes (categories A1, A2, and A4), each corresponding to an electrophysiologically identified receptor class, and (ii) that the N-methyl aspartate (A1) and quisqualate (A2) receptor types are selectively associated with PSDs. L-[3H]Glutamate bound to an apparently homogeneous population of sites in PSDs with a Kd of 3.39 X 10(-7) M and a Bmax (maximum number of binding sites) of 6.1 pmol/mg of protein. Inhibition studies demonstrated that these sites could be resolved into two distinct subtypes. N-Methyl aspartate maximally inhibited 58% of PSD-located L-glutamate binding sites with a Ki of 7.2 X 10(-6) M (the A1 site), and quisqualate inhibited 42% with a Ki of 1.1 X 10(-6) M (the A2 site); the effects of both substances were additive. Experiments with a range of acidic amino acid analogues indicated that the ligand selectivities of these two binding sites conformed to those of the N-methyl D-aspartate and quisqualate receptor classes defined electrophysiologically. The Cl--dependent population of L-glutamate binding sites (the A4 site), which predominates in synaptic membranes, was absent from isolated PSDs.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D007700:Kinetics; D008297:Male; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000378:metabolism*; D016318:Quisqualic Acid; D051381:Rats; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism*
D000596:Amino Acids; D002712:Chlorides; D005971:Glutamates; D010069:Oxadiazoles; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid