PREFERENTIAL LOCATION OF N-METHYL-D-ASPARTATE (NMDA) RECEPTORS ON POSTSYNAPTIC MEMBRANES AND ON NONNORADRENERGIC NERVE-TERMINALS OF THE RAT-BRAIN CORTEX

The effect of DSP4-induced destruction of noradrenergic neurones on H-3-3-(2-carboxypiperazine-4-yl) propyl-1-phosphonic acid (H-3-CPP) binding to N-methyl-D-aspartate (NMDA) receptors and on H-3-desipramine (H-3-DMI) binding to the neuronal noradrenaline carrier was investigated in rat brain cortex buffy coat membranes. H-3-DMI bound with high affinity to a single site at the neuronal noradrenaline carrier (K(D) = 5.26+/-1.67 nmol/1) whereas the binding of H-3-CPP to the NMDA receptor was of intermediate affinity (K(D) = 274+/-45 nmol/1). Fourteen days after a single-dose treatment with DSP4 (1) the B(max) value for H-3-DMI binding was reduced by 74%, (2) the B(max) value for H-3-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 H-3-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 H-3-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.