Identification and characterization of a high-affinity glutamate-controlled TCP binding site in rat brain postsynaptic densities.
The kinetic and equilibrium binding parameters of the phencyclidine receptor ligand [3H]N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) to a postsynaptic density (PSD) subcellular fraction from rat brain were investigated. A single site was found, which was identified as the high-affinity TCP binding site by competition with dibenzocycloalkenimine (MK-801). In contrast, [3H]TCP binds to two sites on the plasma membrane fraction used as a precursor for PSD; on both fractions, [3H]TCP binding responds to glutamate by an increase of the association rate, the dissociation constant and the number of sites being unchanged. In the PSD fraction [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), an antagonist specific for the N-methyl-D-aspartate (NMDA) site, bound to high- and low-affinity sites. These results ascertain the presence and identity of synaptic NMDA-gated ion channels, which are assumed in the current hypothesis about excitotoxicity, long-term potentiation and learning.
Foucaud
B
B
Centre de Neurochimie du CNRS, Strasbourg, France.
Gombos
G
G
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D007700:Kinetics; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D017478:Receptors, Phencyclidine; D013347:Subcellular Fractions / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D005971:Glutamates; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; C012058:tenocyclidine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D010622:Phencyclidine