Article: Radioligand binding studies reveal agmatine is a more selective antagonist for a polyamine-site on the NMDA receptor than arcaine or ifenprodil.
2002 Volume 952, Issue 1, Page(s) 71–77
Abstract: Ifenprodil, arcaine and agmatine have all been reported to inhibit the NMDA receptor by actions at polyamine-sites, however the specific sites with which these compounds interact is unknown. Here we used radioligand binding of [3H]MK-801 to a membrane ... ...
Abstract | Ifenprodil, arcaine and agmatine have all been reported to inhibit the NMDA receptor by actions at polyamine-sites, however the specific sites with which these compounds interact is unknown. Here we used radioligand binding of [3H]MK-801 to a membrane preparation from rat cerebral cortex to investigate the interactions of these compounds with the NMDA receptor complex. In the absence of exogenous polyamines, agmatine reduced [3H]MK-801 binding only at concentrations over 500 micro M, as opposed to the putative polyamine-site antagonists arcaine and ifenprodil which directly reduce ligand binding at much lower concentrations (5 micro M) in the absence of polyamines. In our studies, all three compounds significantly reduced spermidine-potentiated [3H]MK-801 binding, however agmatine was the only compound effective at concentrations below those that produced direct inhibition of [3H]MK-801 binding. Under these conditions, agmatine had a K(i)=14.8 micro M for spermidine-potentiated [3H]MK-801 binding and displayed characteristics of a competitive antagonist. Agmatine, as well as ifenprodil and arcaine, also displaced [3H]spermidine from rat cortical membranes at concentrations similar to those that were effective at reducing spermidine-potentiated [3H]MK-801 binding. In conclusion, these data suggest that agmatine reduces the potentiating effects of polyamines by competitive antagonism at a specific site on the NMDA receptor complex, and that these actions of agmatine differ from those of ifenprodil and arcaine. |
---|---|
MeSH term(s) | Agmatine/metabolism ; Agmatine/pharmacology ; Animals ; Biguanides/metabolism ; Biguanides/pharmacology ; Binding Sites/drug effects ; Binding, Competitive ; Dizocilpine Maleate/metabolism ; Dizocilpine Maleate/pharmacology ; Excitatory Amino Acid Antagonists/metabolism ; Excitatory Amino Acid Antagonists/pharmacology ; Male ; Piperidines/metabolism ; Piperidines/pharmacology ; Radioligand Assay ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/chemistry ; Receptors, N-Methyl-D-Aspartate/metabolism ; Spermidine/metabolism ; Spermidine/pharmacology ; Tritium |
Chemical Substances | Biguanides ; Excitatory Amino Acid Antagonists ; Piperidines ; Receptors, N-Methyl-D-Aspartate ; Tritium (10028-17-8) ; arcaine (544-05-8) ; Dizocilpine Maleate (6LR8C1B66Q) ; Agmatine (70J407ZL5Q) ; ifenprodil (R8OE3P6O5S) ; Spermidine (U87FK77H25) |
Language | English |
Publishing date | 2002-09-27 |
Publishing country | Netherlands |
Document type | Comparative Study ; Journal Article ; Research Support, U.S. Gov't, P.H.S. |
ZDB-ID | 1200-2 |
ISSN | 1872-6240 ; 0006-8993 |
ISSN (online) | 1872-6240 |
ISSN | 0006-8993 |
DOI | 10.1016/s0006-8993(02)03198-0 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
Full text online
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
Zs.A 161: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.