Heterogeneity of NMDA receptors labelled with [3H]3-((±)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP): receptor status in Alzheimer's disease brains

The binding of [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP) was studied in rat and human brain synaptic membranes. Specific binding was saturable, reversible and inhibited by a range of compounds active at N-methyl-D-aspartate (NMDA) receptors such as 2-amino-5-phosphonopentanoate (AP5), 2-amino-7-phosphonoheptanoate (AP7), NMDA and cis-2,4-methanoglutamate. Binding was heterogeneous as evidenced by non-linear Scatchard plots and Hill coefficients for binding inhibitors significantly different from unity. LIGAND analysis of the binding data indicated the likely presence of two distinct binding components for CPP, one of high (Kd values approx. = 70 nM) and the other of low (Kd values approx. 5 μM) affinity. Possible alterations in the binding of [3H]CPP to either site were investigated in medial frontal and medial temporal cortex from Alzheimer's disease brains and compared with control tissues, carefully matched for age and postmortem delay. While there were considerable inter-individual variations in binding, no significant differences were detected either between brain regions in either Alzheimer or control subjects, or between Alzheimer's disease and control brains. These data suggest the presence of at least two components of [3H]CPP binding in both rat and human brain tissue. The integrity of neither of these components is altered in Alzheimer's disease, consistent with a lack of gross alterations of NMDA receptors in this disorder.