Preferential location of N-methyl-D-aspartate (NMDA) receptors on postsynaptic membranes and on non-noradrenergic nerve terminals of the rat brain cortex.
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.
Fink
K
K
Institut für Pharmakologie und Toxikologie, Rheinischen Friedrich-Wilhelms-Universität Bonn, Federal Republic of Germany.
Blohm
M
M
Molderings
G
G
Bönisch
H
H
Göthert
M
M
D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003891:Desipramine / Q000378:metabolism; D008297:Male; D009411:Nerve Endings / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013566:Sympathomimetics / Q000378:metabolism
D001596:Benzylamines; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D013566:Sympathomimetics; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C012102:DSP 4; D003891:Desipramine; D009638:Norepinephrine