Preferential location of N-methyl-D-aspartate (NMDA) receptors on postsynaptic membranes and on non-noradrenergic nerve terminals of the rat brain cortex

Abstract

The effect of DSP4-induced destruction of noradrenergic neurones on 3H-3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (3H-CPP) binding to N-methyl-D-aspartate (NMDA) receptors and on 3H-desipramine (3H-DMI) binding to the neuronal noradrenaline carrier was investigated in rat brain cortex buffy coat membranes. 3H-DMI bound with high affinity to a single site at the neuronal noradrenaline carrier (KD = 5.26 +/- 1.67 nmol/l) whereas the binding of 3H-CPP to the NMDA receptor was of intermediate affinity (KD = 274 +/- 45 nmol/l). Fourteen days after a single-dose treatment with DSP4 (1) the Bmax value for 3H-DMI binding was reduced by 74%, (2) the Bmax value for 3H-CPP binding only tended to be decreased (by 24%; not statistically significant), (3) the endogenous noradrenaline content was reduced by 70% compared to untreated controls and, (4) the absolute amount of the NMDA-evoked 3H-noradrenaline overflow but not the fractional release was reduced by 55%. It is concluded that in the rat cerebral cortex presynaptic NMDA-receptors on noradrenergic nerve endings, which have previously been detected in release experiments with NMDA on cortical synaptosomes preincubated with 3H-noradrenaline, cannot be identified in radioligand binding experiments. Obviously, the cerebral cortical NMDA receptors are predominantly located on postsynaptic neuronal membranes and potentially on non-noradrenergic nerve terminals as well.