Glycine reverses 7-chlorokynurenic acid-induced inhibition of [3H]MK-801 binding.
7-Chlorokynurenic acid (7-Cl KYNA) has been reported to attenuate N-methyl-D-aspartate (NMDA) receptor functioning by a potent and selective inhibitory action mediated at the strychnine-insensitive glycine recognition site of the NMDA complex. Here we report that 7-Cl KYNA dose-dependently inhibits [3H]MK-801 binding to the PCP receptor, and that this effect is reversed by addition of glycine. Since [3H]MK-801 binding is a measure of channel activation, our results are consistent with the hypotheses that 7-Cl KYNA exerts its NMDA receptor antagonism by acting at the glycine site, and that activation of the glycine site is required for NMDA channel activity to occur.
Sircar
R
R
Department of Psychiatry, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10461.
Frusciante
M J
MJ
Javitt
D C
DC
Zukin
S R
SR
D000818:Animals; D003986:Dibenzocycloheptenes / Q000378:metabolism*; D016291:Dizocilpine Maleate; D005998:Glycine / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D017478:Receptors, Phencyclidine
D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid; D005998:Glycine