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.
MeSH terms
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Animals
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Aspartic Acid / analogs & derivatives
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Aspartic Acid / pharmacology
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Cerebellum / drug effects
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Cerebellum / physiology*
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Cyclic GMP / biosynthesis*
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Cycloserine / pharmacology
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Dibenzocycloheptenes / pharmacology
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Dizocilpine Maleate
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Male
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Mice
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N-Methylaspartate
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Neurons / drug effects
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Neurons / physiology*
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Piperazines / pharmacology
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Pyrrolidinones / pharmacology
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Receptors, Glycine
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Receptors, N-Methyl-D-Aspartate
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Receptors, Neurotransmitter / drug effects
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Receptors, Neurotransmitter / physiology*
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Serine / antagonists & inhibitors
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Serine / pharmacology*
Substances
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Dibenzocycloheptenes
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Piperazines
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Pyrrolidinones
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Receptors, Glycine
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Receptors, N-Methyl-D-Aspartate
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Receptors, Neurotransmitter
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Aspartic Acid
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Serine
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N-Methylaspartate
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Dizocilpine Maleate
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Cycloserine
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3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
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1-hydroxy-3-amino-2-pyrrolidone
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Cyclic GMP