Radioligand binding studies reveal agmatine is a more selective antagonist for a polyamine-site on the NMDA receptor than arcaine or ifenprodil
- PMID:12363406
- DOI: 10.1016/s0006-8993(02)03198-0
Radioligand binding studies reveal agmatine is a more selective antagonist for a polyamine-site on the NMDA receptor than arcaine or ifenprodil
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.
Similar articles
- Arcaine uncovers dual interactions of polyamines with the N-methyl-D-aspartate receptor.Reynolds IJ.Reynolds IJ.J Pharmacol Exp Ther. 1990 Dec;255(3):1001-7.J Pharmacol Exp Ther. 1990.PMID:2148185
- Neomycin is an agonist at a polyamine site on the N-methyl-D-aspartate receptor.Pullan LM, Stumpo RJ, Powel RJ, Paschetto KA, Britt M.Pullan LM, et al.J Neurochem. 1992 Dec;59(6):2087-93. doi: 10.1111/j.1471-4159.1992.tb10099.x.J Neurochem. 1992.PMID:1359015
- Effects of ifenprodil on the N-methyl-D-aspartate receptor ionophore complex in rat brain.Ogita K, Ohkawara A, Suzuki T, Ohgaki T, Uchida S, Meguri H, Yoneda Y.Ogita K, et al.Neurochem Int. 1992 Jul;21(1):135-47. doi: 10.1016/0197-0186(92)90076-4.Neurochem Int. 1992.PMID:1363860
- Modulation of the NMDA receptor by polyamines.Williams K, Romano C, Dichter MA, Molinoff PB.Williams K, et al.Life Sci. 1991;48(6):469-98. doi: 10.1016/0024-3205(91)90463-l.Life Sci. 1991.PMID:1825128Review.
- Ifenprodil, a novel NMDA receptor antagonist: site and mechanism of action.Williams K.Williams K.Curr Drug Targets. 2001 Sep;2(3):285-98. doi: 10.2174/1389450013348489.Curr Drug Targets. 2001.PMID:11554553Review.
Cited by
- Agmatine reduces ultrasonic vocalization deficits in female rat pups exposed neonatally to ethanol.Wellmann K, Lewis B, Barron S.Wellmann K, et al.Neurotoxicol Teratol. 2010 Mar-Apr;32(2):158-63. doi: 10.1016/j.ntt.2009.11.005. Epub 2009 Nov 27.Neurotoxicol Teratol. 2010.PMID:19945529Free PMC article.
- Polyamine modulation of NMDARs as a mechanism to reduce effects of alcohol dependence.Barron S, Lewis B, Wellmann K, Carter M, Farook J, Ring J, Rogers DT, Holley R, Crooks P, Littleton J.Barron S, et al.Recent Pat CNS Drug Discov. 2012 Aug;7(2):129-44. doi: 10.2174/157488912800673128.Recent Pat CNS Drug Discov. 2012.PMID:22574674Free PMC article.Review.
- Agmatine enhances the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshock seizure model.Luszczki JJ, Czernecki R, Wojtal K, Borowicz KK, Czuczwar SJ.Luszczki JJ, et al.J Neural Transm (Vienna). 2008 Nov;115(11):1485-94. doi: 10.1007/s00702-008-0046-3. Epub 2008 Apr 1.J Neural Transm (Vienna). 2008.PMID:18379717
- Nitric oxide is involved in the memory facilitation induced by spermidine in rats.Guerra GP, Mello CF, Sauzem PD, Berlese DB, Furian AF, Tabarelli Z, Rubin MA.Guerra GP, et al.Psychopharmacology (Berl). 2006 Jun;186(2):150-8. doi: 10.1007/s00213-006-0376-5. Epub 2006 Apr 7.Psychopharmacology (Berl). 2006.PMID:16601997
- Agmatine requires GluN2B-containing NMDA receptors to inhibit the development of neuropathic pain.Peterson CD, Kitto KF, Verma H, Pflepsen K, Delpire E, Wilcox GL, Fairbanks CA.Peterson CD, et al.Mol Pain. 2021 Jan-Dec;17:17448069211029171. doi: 10.1177/17448069211029171.Mol Pain. 2021.PMID:34210178Free PMC article.
Publication types
MeSH terms
Substances
Related information
Grants and funding
LinkOut - more resources
Full Text Sources