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Journal of Neuroscience, Vol 8, 493-501, Copyright © 1988 by Society for Neuroscience
Anatomic correlation of NMDA and 3H-TCP-labeled receptors in rat brain
WF Maragos, JB Penney and AB Young
Department of Neurology, University of Michigan, Ann Arbor 48104.
Using quantitative autoradiography, we have compared the regional
distribution of N-methyl-D-aspartate (NMDA) receptors labeled with 3H-
glutamate and dissociative anesthetic binding sites labeled with 3H-N-
(1-[2-thienyl]cyclohexyl)3,4-piperidine (3H-TCP). Binding of both ligands
was highest in the hippocampal formation, with high concentrations in a
number of cortical and olfactory regions. Intermediate amounts of binding
for both ligands were measured in several thalamic and basal telencephalic
structures. Very little binding was observed in the hypothalamus, some deep
forebrain regions, and most brain-stem structures. Linear-regression
analysis comparing the binding at both sites revealed a marked concordance
(R = 0.95; p less than 0.001; Pearson product-moment). The granule cell
layer of the cerebellum was the only region in which this concordance was
not observed. Scatchard analysis of 3H-glutamate binding to NMDA receptors
in stratum radiatum of hippocampal formation revealed an apparent single
binding site with a Bmax of 9.78 +/- 0.84 pmol/mg protein and KD of 158 +/-
37 nM. 3H-TCP also bound to an apparent single site with a Bmax of 2.07 +/-
0.16 pmol/mg protein and KD of 127 +/- 30 nM. Our results are consistent
with the hypothesis that the dissociative anesthetic binding site is linked
to the NMDA receptor, and the data suggest that there are approximately 4-5
NMDA binding sites for each dissociative anesthetic binding site.
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