Regionally different N‐methyl‐D‐aspartate receptors distinguished by ligand binding and quantitative autoradiography of [³H]‐CGP 39653 in rat brain

Abstract

Binding of D,L-(E)-2-amino-4-[3H]-propyl-5-phosphono-3-pentenoic acid ([3H]showed that the inhibition was lower in striatum (72% of control), with respect to cortex (66% of control) and hippocampal formation (58% of control).6 The inhibitory action of 10 gM glycine was reversed by 100 gM 7-chloro-kynurenic acid (7-CKA), a competitive antagonist of the glycine site of the NMDA receptor channel complex, in all areas tested. Moreover, reversal by 7-CKA was not the same in all regions (P<0.05, two-ways ANOVA). In fact, in the presence of 10 gM glycine and 100 gM 7-KCA, specific [3H]-CGP 39653 binding in the striatum was 131% of control, which was significantly greater (Fisher's protected LSD) than binding in the hippocampus and the thalamus (104% and 112% of control, respectively).7 These results demonstrate that [3H]-CGP 39653 binding can be inhibited by glycine in rat brain regions containing NMDA receptors; moreover, they suggest the existence of regionally distinct NMDA receptor subtypes with a different allosteric mechanism of [3H]-CGP 39653 binding modulation through the associated glycine site.

Allosteric modulation of [3H]‐CGP39653 binding through the glycine site of the NMDA receptor: further studies in rat and human brain

“…The enhancement was uneven in rat brain: in CPu, for example, the increase was higher than in the cerebral cortex. This was in line with the previous ®nding that 1 mM glycine was able to inhibit basal [ 3 H]-CGP39653 binding to a smaller extent in CPu than in the cerebral cortex (Mugnaini et al, 1996).…”

“…The extent of this eect diered between regions and revealed the existence of NMDA receptor subtypes which may have a dierent sensitivity to endogenous ligands as well as to potential therapeutic agents (Mugnaini et al, 1996). The aim of the present study was to con®rm these ®ndings in rat brain and look for the possible existence of similar NMDA receptor subtypes in human brain.…”

“…It has been shown by in vivo microdialysis that striatum contains a lower level of endogenous free glycine than the cerebral cortex (Globus et al, 1991;Hashimoto et al, 1995), which is the converse of what would be predicted from the present data. Instead they might be explained by considering the regionally dierent potencies of glycine in the allosteric inhibition of [ Mugnaini et al, 1996). On the contrary, there was not any signi®cant variation in anity values of glycine, GV150526A, [ 3 H]-CGP39653 and L-glutamate.…”

“…]-CGP39653 receptor autoradiography was performed as described by Mugnaini et al (1996). Animals were killed by intracardiac perfusion, under urethane anaesthesia (1.5 mg kg…”

Estrogen-like Activity of Tamoxifen and Raloxifene on NMDA Receptor Binding and Expression of its Subunits in Rat Brain

“…Furthermore, the difference between intact and ovariectomized rats observed in the hippocampus is supported by the recent finding that NMDA receptor changes during the estrous cycle (Lu et al 2000). So far, it has been shown that specific L-[ 3 H]CGP 39653 binding is possible only when subunit NMDA receptor 2A is present in the heteromeric receptor (Marti et al 1993;Lynch et al 1994;Laurie and Seeburg 1994;Mugnaini et al 1996).…”