Inhibition of [3H]CGP 39653 binding to NMDA receptors by a P2 antagonist, suramin.
Suramin, which has been used for more than 50 years as an anthelmintic in humans, has recently been shown to inhibit P2 purinoceptors in the CNS and to block glutamate-evoked excitatory potentials in hippocampus. We now report that suramin inhibits (IC50 approximately 100 microM) the binding of [3H]CGP 39653, a ligand specific for NMDA-type glutamate receptors in brain. Consequently, suramin at concentrations used sometimes in physiological experiments may act as both P2x and NMDA antagonist. Since both NMDA receptors and P2x-subtype of purinoceptors form Ca(2+)-selective channels, suramin may block Ca2+ entry into neurones depolarized by either ATP, L-glutamate or any other neurotransmitter or drug acting via P2x or NMDA receptors.
Balcar
V J
VJ
Department of Anatomy and Histology, University of Sydney, NSW, Australia.
Dias
L S
LS
Li
Y
Y
Bennett
M R
MR
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D000871:Anthelmintics / Q000378:metabolism*; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism*; D005260:Female; D005629:Frozen Sections; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D058919:Purinergic P2 Receptor Antagonists; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013498:Suramin / Q000378:metabolism*; D014316:Tritium
D000871:Anthelmintics; D018691:Excitatory Amino Acid Antagonists; D058919:Purinergic P2 Receptor Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; C069052:CGP 39653; D013498:Suramin; D015763:2-Amino-5-phosphonovalerate