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P 2 purinoceptor blocker suramin antagonises NMDA receptors and protects against excitatory behaviour caused by NMDA receptor agonist ( RS )‐(tetrazol‐5‐yl)‐glycine in rats
Author(s) -
Ong WeiYi,
Motin Leonid G.,
Hansen Mitchell A.,
Dias Leonora S.,
Ayrout Chantal,
Bennett Maxwell R.,
Balcar Vladimir J.
Publication year - 1997
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19970901)49:5<627::aid-jnr13>3.0.co;2-s
Subject(s) - suramin , nmda receptor , pharmacology , kainate receptor , agonist , receptor , ionotropic effect , chemistry , biology , ampa receptor , biochemistry
It has been reported that suramin, an anthelminthic, trypanocidal agent and an inhibitor of P 2 receptors, may antagonise N‐methyl‐D‐aspartate (NMDA) subtype of the excitatory amino acid receptors. Both NMDA receptors and P 2X subclass of P 2 receptors are ligand‐gated Ca 2+ ‐selective channels and, since the increased influx of Ca 2+ into neurons has been linked to neurotoxicity, simultaneous inhibition of P 2X and NMDA receptors in vivo by suramin could represent an effective neuroprotective treatment. We have found that suramin inhibited the binding of [ 3 H]CGP 39653 to NMDA receptor binding sites in vitro and reduced the frequency of NMDA channel openings in patch‐clamp studies. Suramin (1 mM) had no effect on [ 3 H]kainate binding in vitro. In vivo, intracerebroventricular (ICV) injections of suramin (70 nmol/brain) antagonised convulsive effects of the NMDA agonist ( RS )‐(tetrazol‐5‐yl)‐glycine (TZG, LY 285265). Suramin, however, did not prevent neurotoxic lesions in the hippocampus caused by ICV administration of TZG. Increasing the dose of suramin resulted in death from severe respiratory depression. J. Neurosci. Res. 49:627–638, 1997. © 1997 Wiley‐Liss, Inc.