Effects of 1-methyl-4-phenylpyridinium on radioligand binding to the NMDA receptor complex.
The present study was performed to determine if 1-methyl-4-phenylpyridinium (MPP+) affects binding of [3H](-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne maleate ([3H]MK-801), [3H]glutamate and [3H]glycine to the rat and monkey striatal N-methyl-D-aspartate (NMDA) receptor. We found that MPP+ non-competitively inhibits [3H]MK-801 binding with IC50 values between 80 and 330 microM depending on the species and the concentration of glutamate and glycine. MPP+ also partially inhibited [3H]glycine binding without affecting [3H]glutamate binding. We conclude that MPP+ is not an agonist at the NMDA receptor but at high concentrations inhibits NMDA receptor function.
Sundström
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Dept. of Clinical Neuroscience and Family Medicine, Karolinska Institutet, Huddinge, Sweden.
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D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D016291:Dizocilpine Maleate / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D015655:1-Methyl-4-phenylpyridinium; D005998:Glycine