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| Content Provider | PubMed Central |
|---|---|
| Author | Foster, A. C. Wong, E. H. |
| Abstract | The influence of endogenous and exogenous acidic amino acids on the binding of [3H]-MK-801, a selective, non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, has been investigated in rat cerebral cortex crude synaptic membranes (CSM). Removal of endogenous glutamate and aspartate from CSM by repeated washing reduced the affinity of [3H]-MK-801 for its binding site (with no change in the total number of binding sites) and increased NMDA-sensitive L-[3H]-glutamate binding. In washed CSM, competitive NMDA antagonists of the DL-alpha-amino-omega-phosphonocarboxylate series reduced [3H]-MK-801 binding and NMDA-sensitive L-[3H]-glutamate binding, the most active compounds being 2-amino-5-phosphonovalerate (AP5) and 2-amino-7-phosphono-heptanoate (AP7). Exogenous excitatory amino acid agonists enhanced the binding of [3H]-MK-801 to washed CSM by up to 700%. A selective involvement of NMDA receptors in these effects was indicated by the excellent correlation between EC50s for stimulation of [3H]-MK-801 binding and IC50s for inhibition of NMDA-sensitive L-[3H]-glutamate binding in the same membranes. The selective, competitive NMDA receptor antagonist D-AP5 blocked the L-glutamate-induced increase in [3H]-MK-801 binding in a competitive manner with a pA2 value of 6.0. These results seem to reflect a molecular interaction between two distinct components of the NMDA receptor complex: the transmitter recognition site and the site through which MK-801 exerts its antagonist effects, possibly the ion channel. |
| Starting Page | 403 |
| File Format | |
| ISSN | 00071188 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 91 |
| Language | English |
| Publisher Date | 1987-06-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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