Anatomic correlation of NMDA and 3H-TCP-labeled receptors in rat brain

Abstract

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.

Localization of NMDA receptors in the cerebral cortex: a schematic overview

“…Electron microscopic immunocytochemical studies have shown that both NR1 and NR2A/B IRs are mostly present on dendrites and dendritic spines (21,23,24,31,32). This observation is consistent with i) the location of axon terminals forming asymmetric synapses (34) and the nature and location of Glu+ axon terminals (35,36); ii) previous indications from radioligand binding (37)(38)(39)(40)(41) and in situ hybridization (8; for a discussion, see 22) studies, and iii) the results of electrophysiological (42) and combined electrophysiologicalCa 2+ imaging investigations (43). Overall, this evidence indicates that the bulk of the effects of NMDA receptor activation is generated at distal dendrites and spines, and supports the view expressed by several investigators that dendritic spines in cortical neurons are the site of biophysical events underlying complex integrative properties of cortical neurons (44)(45)(46)(47)(48).…”

Nebracetam (WEB 1881FU) Prevents N-Methyl-D-Aspartate Receptor-Mediated Neurotoxicity in Rat Striatal Slices

“…We have shown that either high K+ or en dothelin participates in the development of hypoglycemia or hypoglycemia/hypoxia-induced brain damage through the VOCC in an in vitro model by directly monitoring the real-time dynamics of dopamine (DA) released from striatal slices (2,3). The striatum has been known to be highly vulnerable to hypoxia/ischemia (4) and contains NMDA receptors and 1,4-dihydropyridine binding sites labeling VOCC with a moderate density (5,6). Therefore, an in vitro model of brain damage we designed may be useful for determining the develop ment of brain damage through receptor-operated Ca 2+ channels as well as VOCC.…”

Effects of the New Anti-Ulcer Drug Ecabet Sodium (TA-2711) on Pepsin Activity I. Inactivation of Enzyme Protein

“…Recent auto radiographic studies have revealed that NMDA recep tors are present at higher density in the CAI region and the dentate gyrus of the hippocampus (14)(15)(16). Prop erties of NMDA receptor-mediated synaptic responses in the hippocampus have been studied extensively in the Schaffer collateral-CAI pyramidal cell synapses, but are not well studied in the perforant path-dentate gyrus gran ule cell synapses.…”