cgp-39653 and 3-(2-carboxypiperazine-4-yl)propyl-1-phosphate

A complex of four proteins isolated from neuronal membranes has ligand binding sites for N-methyl-d-aspartate (NMDA) receptor agonists and antagonists and forms NMDA-activated ion channels upon reconstitution into lipid membranes. In this study, the cDNA of a subunit of this complex containing binding sites for the competitive antagonists of NMDA receptors was cloned. The cDNA clone coded for a protein of 719 amino acids (78.9 kDa). The expressed protein had binding activity for the agonists l-[3H]glutamate and [3H]glycine, the antagonist (+/-)-[3H]-(E)-2-amino-4-propyl-5-phosphonopentanoic acid ([3H]CGP 39653), but not the ion channel inhibitors. The cloned cDNA had no homology to other cloned cDNAs. Northern blot analyses indicated high expression of an 3.8 kb poly(A+) RNA in brain, but not in other tissues. These findings indicate that proteins that have recognition sites for NMDA receptor activators and inhibitors and that differ from the well-characterized NMDA receptor proteins NR1-3 are expressed in mammalian brain.

Topics: 2-Amino-5-phosphonovalerate; Amino Acid Sequence; Animals; Base Sequence; Carrier Proteins; Cloning, Molecular; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Hippocampus; Male; Molecular Sequence Data; N-Methylaspartate; Nerve Tissue Proteins; Piperazines; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate