title: Evidence for direct interactions between the NMDA and glycine recognition sites in brain.
abstract: The interaction between glycine and competitive N-methyl-D-aspartate (NMDA) antagonists was investigated. Glycine (IC50 = 170 nM) partially (approximately 60%) inhibited [3H]CGS-19755 ((+/-)-4-phosphonomethyl-2-piperdine carboxylic acid), but not [3H]CPP (3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) binding. The action of glycine was mimicked by D-serine and antagonized by 7-chlorokynurenate. CGS-19755 (IC50 = 230 nM) partially inhibited [3H]glycine binding from strychnine-insensitive sites; this effect was antagonized by NMDA. CPP and NPC 12626 (2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid) inhibited [3H]glycine binding, but only at concentrations 100- to 1000-fold greater than required to displace [3H]CGS-19755 or [3H]CPP. These data provide the first evidence for bidirectional interactions between glycine and NMDA recognition sites and suggest pharmacological differences among competitive NMDA antagonists.
authors.affiliation: Nova Pharmaceutical Corporation, CNS Research, Baltimore, MD 21224-2788.
authors.forename: P V
authors.initials: PV
authors.lastname: Kaplita
authors.forename: J W
authors.initials: JW
authors.lastname: Ferkany
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D010875:Pipecolic Acids; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012694:Serine / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D010875:Pipecolic Acids; D010879:Piperazines; D010880:Piperidines; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C060212:NPC 12626; D012694:Serine; C053672:selfotel; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid