3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid recognizes two N-methyl-D-aspartate binding sites in rat cerebral cortex membranes.
Binding of 3-[(+-)-2-carboxypiperazin-4-yl][3H]-propyl-1-phosphonic acid ([3H]CPP), a competitive inhibitor of N-methyl-D-aspartate (NMDA), has been studied in synaptic plasma membranes from rat cerebral cortex. Computer analysis of saturation and homologous displacement isotherms deriving from these plasma membranes indicated the existence of two binding sites: a specific, saturable, high-affinity binding site with a pKD value of 7.53 +/- 0.03 (29.5 nM) and a maximum binding value (Bmax) of 2.25 +/- 0.36 pmol/mg of protein, and a low-affinity site with a KD of approximately 600 nM and a Bmax of 7.0 pmol/mg of protein. It is argued that, in the light of current literature evidence, the low-affinity binding site may represent an agonist-dependent receptor, linked to physiological processes such as neurotransmitter release and channel regulation, whereas the high-affinity binding site may be linked to an antagonist-preferred receptor, for which no function has yet been reported.
van Amsterdam
F T
FT
Glaxo Research Laboratories, Department of Biochemistry, Verona, Italy.
Giberti
A
A
Mugnaini
M
M
Ratti
E
E
D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism
D005971:Glutamates; D018377:Neurotransmitter Agents; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid