Spermidine enhancement of [3H]MK-801 binding to the NMDA receptor complex in human cortical membranes.
The effects of spermidine on the binding of [3H]MK-801 to the N-methyl-D-aspartate (NMDA) receptor complex was studied in human cerebral cortical membranes. [3H]MK-801 binding was increased from 56 +/- 5 fmol/mg protein (mean +/- S.E.M., n = 7) to 319 +/- 71 fmol/mg protein in the presence of 200 microM spermidine. The ED50 for spermidine stimulation of [3H]MK-801 binding was 89 +/- 22 microM (mean +/- S.E.M., n = 6). In the presence of glutamate (1 microM) plus glycine (1 microM) the ED50 was reduced to 5.5 +/- 0.7 microM. The increase in binding in the presence of spermidine was characterised by an increase in the rate of association of [3H]MK-801. In the presence of spermidine. [3H]MK-801 was inhibited by AP5. 7-chlorokynurenic acid and ifenprodil with IC50 values of 0.5 +/- 0.3 24 +/- 19 and 91 +/- 28 microM, respectively. None of these antagonists was a competitive inhibitor of the spermidine stimulation of [3H]MK-801 binding. Thus spermidine modulates the NMDA receptor complex in human brain, providing further evidence that the complex is similar in rat and human cortex.
Steele
J E
JE
Department of Neurochemistry, Institute of Neurology, London, U.K.
Bowen
D M
DM
Francis
P T
PT
Green
A R
AR
Cross
A J
AJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011869:Radioligand Assay; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013095:Spermidine / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D010880:Piperidines; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid; C010739:ifenprodil; C057013:7-chlorokynurenic acid; D013095:Spermidine