The glycine antagonist 7-chlorokynurenic acid blocks the effects of N-methyl-D-aspartate on agonist-stimulated phosphoinositide hydrolysis in guinea-pig brain slices.
Despite having no effect on basal phosphoinositide hydrolysis. N-methyl-D-aspartate (NMDA) inhibited carbachol-stimulated accumulation of 3H-inositol phosphates and enhanced that due to noradrenaline in guinea-pig cerebral cortex slices. The glycine antagonist 7-chlorokynurenic acid inhibited the effects of NMDA and this inhibition was reversed by glycine. The action of 7-chlorokynurenic acid was not mimicked by strychnine or HA 966 (1-hydroxy-3-aminopyrrolid-2-one). L-Glutamate also inhibited carbachol-stimulated accumulation of 3H-inositol phosphates, but this inhibition was not blocked by 7-chlorokynurenic acid. The data are consistent with glycine maintaining tonic control over NMDA receptor activity in guinea-pig brain.
Kendall
D A
DA
Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre, England.
Robinson
J P
JP
D000818:Animals; D001921:Brain / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D006168:Guinea Pigs; D006868:Hydrolysis; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D005971:Glutamates; D010716:Phosphatidylinositols; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid; D005998:Glycine