Tags

Type your tag names separated by a space and hit enter

Radioligand binding studies reveal agmatine is a more selective antagonist for a polyamine-site on the NMDA receptor than arcaine or ifenprodil.
Brain Res. 2002 Oct 11; 952(1):71-7.BR

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.

Authors+Show Affiliations

Gibson DA
Department of Molecular and Biomedical Pharmacology, University of Kentucky, Cooper and University Drives, Lexington, KY 40546-0236, USA. dagibs2@uky.edu
Harris BR
No affiliation info available
Rogers DT
No affiliation info available
Littleton JM
No affiliation info available

MeSH

AgmatineAnimalsBiguanidesBinding SitesBinding, CompetitiveDizocilpine MaleateExcitatory Amino Acid AntagonistsMalePiperidinesRadioligand AssayRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSpermidineTritium

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12363406

Citation

Gibson, D Alex, et al. "Radioligand Binding Studies Reveal Agmatine Is a More Selective Antagonist for a Polyamine-site On the NMDA Receptor Than Arcaine or Ifenprodil." Brain Research, vol. 952, no. 1, 2002, pp. 71-7.
Gibson DA, Harris BR, Rogers DT, et al. Radioligand binding studies reveal agmatine is a more selective antagonist for a polyamine-site on the NMDA receptor than arcaine or ifenprodil. Brain Res. 2002;952(1):71-7.
Gibson, D. A., Harris, B. R., Rogers, D. T., & Littleton, J. M. (2002). Radioligand binding studies reveal agmatine is a more selective antagonist for a polyamine-site on the NMDA receptor than arcaine or ifenprodil. Brain Research, 952(1), 71-7.
Gibson DA, et al. Radioligand Binding Studies Reveal Agmatine Is a More Selective Antagonist for a Polyamine-site On the NMDA Receptor Than Arcaine or Ifenprodil. Brain Res. 2002 Oct 11;952(1):71-7. PubMed PMID: 12363406.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Radioligand binding studies reveal agmatine is a more selective antagonist for a polyamine-site on the NMDA receptor than arcaine or ifenprodil. AU - Gibson,D Alex, AU - Harris,Barton R, AU - Rogers,D Trent, AU - Littleton,John M, PY - 2002/10/5/pubmed PY - 2002/12/11/medline PY - 2002/10/5/entrez SP - 71 EP - 7 JF - Brain research JO - Brain Res VL - 952 IS - 1 N2 - 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. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/12363406/Radioligand_binding_studies_reveal_agmatine_is_a_more_selective_antagonist_for_a_polyamine_site_on_the_NMDA_receptor_than_arcaine_or_ifenprodil_ DB - PRIME DP - Unbound Medicine ER -