(+)-[3H]MK-801 binding sites in postmortem human brain.
The pharmacological specificity and the regional distribution of the N-methyl-D-aspartate receptor-associated 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) binding sites in human postmortem brain tissue were determined by binding studies using (+)-[3H]MK-801. Scatchard analysis revealed a high-affinity (KD = 0.9 +/- 0.2 nM, Bmax = 499 +/- 33 fmol/mg of protein) and a low-affinity (KD = 3.6 +/- 0.9 nM, Bmax = 194 +/- 44 fmol/mg of protein) binding site. The high-affinity site showed a different regional distribution of receptor density (cortex greater than hippocampus greater than striatum) compared to the low-affinity binding site (cerebellum greater than brainstem). The rank order pharmacological specificity and stereoselectivity of the high-(cortex) and low-(cerebellar) affinity binding sites were identical. However, all compounds tested showed greater potency at the high-affinity site in cortex. The results indicate that (+)-[3H]MK-801 binding in human postmortem brain tissue shows pharmacological and regional specificity.
Quarum
M L
ML
Vollum Institute, Oregon Health Sciences University, Portland.
Parker
J D
JD
Keana
J F
JF
Weber
E
E
D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000502:physiology; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D003986:Dibenzocycloheptenes / Q000378:metabolism*; D016291:Dizocilpine Maleate; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016202:N-Methylaspartate; D011180:Postmortem Changes; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D017478:Receptors, Phencyclidine; D013237:Stereoisomerism; D014018:Tissue Distribution; D014316:Tritium
D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D014316:Tritium; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate