In Vivo Modulation of the N-Methyl-D-Aspartate Receptor Complex by D-Serine: Potentiation of Ongoing Neuronal Activity as Evidenced by Increased Cerebellar Cyclic GMP |
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Authors: | Paul L. Wood Mark R. Emmett Tadimeti S. Rao Steve Mick Julie Cler Smriti Iyengar |
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Affiliation: | CNS Diseases Research, G.D. Searle and Company, St. Louis, MO 63198. |
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Abstract: | Direct intracerebellar injections of N-methyl-D-aspartate (NMDA) or D-serine elicited dose-dependent increases in cerebellar cyclic GMP levels, in vivo in the mouse. The actions of D-serine were antagonized by the competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid and by the phencyclidine receptor agonist MK-801, observations supporting actions at the NMDA-coupled glycine receptor. In addition, the actions of D-serine were antagonized by a partial agonist (D-cycloserine) and an antagonist (HA-966) of the NMDA-coupled glycine receptor. These data are all consistent with D-serine acting at the NMDA-coupled glycine receptor and represent the first demonstration of glycine receptor potentiation of ongoing NMDA-mediated neuronal activity in the CNS, rather than potentiation of exogenous NMDA. |
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Keywords: | D-Serine Cerebellar cyclic GMP N-methyl-D-aspar-tate-coupled glycine receptor 3-(2-Carboxypiperazin-4-yl)propyl-1 -phosphonic acid 1 -Hydroxy-3-aminopyrrolidone-2 D-Cyclo-serine MK-801 |
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