title: Modulation of the NMDA receptor by D-serine in the cortex and the spinal cord, in vitro.
abstract: We present a comparative study of the modulation of the N-methyl-D-aspartate (NMDA) receptor at the strychnine-insensitive glycine site in the spinal cord and in the cortex. The excitatory effect of NMDA was potentiated by D-serine (a glycine mimetic) in the hemisected rat spinal cord. The non-competitive NMDA antagonists 7-chlorokynurenic acid (7-Cl KYNA; 10 microM) and 3-amino-1-hydroxypyrrolid-2-one (HA-966; 100 or 200 microM) antagonized the effect of NMDA in the spinal cord and cortical wedge preparation. The antagonism was reversed by the addition of D-serine. This effect was strychnine-insensitive and hence not related to the inhibitory glycine receptor known to be present in the spinal cord. Our results suggest strongly that glycine positively modulates the NMDA system not only at a supraspinal level but also at the spinal level. As the positive modulation of NMDA responses by D-serine was also seen in the presence of tetrodotoxin, we conclude that the NMDA/glycine complex is (also) located on motoneurones in addition to the known glycine-mediated inhibitory system.
authors: Research and Development Department, Ciba-Geigy, Ltd., Basel, Switzerland.
authors: F
authors: F
authors: Brugger
authors: U
authors: U
authors: Wicki
authors: D
authors: D
authors: Nassenstein-Elton
authors: G E
authors: GE
authors: Fagg
authors: H R
authors: HR
authors: Olpe
authors: M F
authors: MF
authors: Pozza
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D012694:Serine / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013331:Strychnine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; D013779:Tetrodotoxin; D012694:Serine; C001369:1-hydroxy-3-amino-2-pyrrolidone; D007736:Kynurenic Acid; D013331:Strychnine; C057013:7-chlorokynurenic acid