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[ 3 H] N ‐[1‐(2‐Thienyl)cyclohexyl]‐3,4‐Piperidine ([ 3 H]TCP) Binding in Human Frontal Cortex: Decreases in Alzheimer‐Type Dementia
Author(s) -
Ninomiya Haruaki,
Fukunaga Reiko,
Taniguchi Takashi,
Fujiwara Motohatsu,
Shimohama Shun,
Kameyama Masakuni
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb01903.x
Subject(s) - nmda receptor , chemistry , dissociation constant , receptor , glutamate receptor , binding site , endocrinology , medicine , cerebral cortex , stereochemistry , biochemistry , biology
We studied [ 3 H] N ‐[1‐(2‐thienyl)cyclohexyl]‐3,4‐piperidine ([ 3 H]TCP) binding to human frontal cortex obtained at autopsy from 10 histologically normal controls and eight histopathologically verified cases with Alzheimer‐type dementia (ATD). Extensively washed membrane preparations were used to minimize the effects of endogenous substances. In ATD frontal cortex, the total concentration ( B max ) of [ 3 H]TCP binding sites was significantly reduced by 40–50%. The apparent dissociation constant ( K D ) values showed no significant change. The reduction in binding capacity was also apparent in Triton X‐100–treated membrane preparations, and there was a linear correlation between the number of [ 3 H]TCP binding sites and that of N ‐methyl‐D‐aspartate (NMDA)‐sensitive [ 3 H]glutamate binding sites. [ 3 H]TCP binding sites spared in ATD brains retained the affinity for the ligand and the reactivity to NMDA, L‐glutamate, and glycine. These results suggest that the primary change in NMDA receptor‐ion channel complex in ATD brains is the reduction of its number, possibly reflecting the loss of neurons bearing these receptor complexes, and that the functional linkage within the receptor complexes spared in ATD brains remains normal.