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

J Neurochem. 1989 Sep;53(3):979-81. doi: 10.1111/j.1471-4159.1989.tb11803.x.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / pharmacology
  • Cerebellum / drug effects
  • Cerebellum / physiology*
  • Cyclic GMP / biosynthesis*
  • Cycloserine / pharmacology
  • Dibenzocycloheptenes / pharmacology
  • Dizocilpine Maleate
  • Male
  • Mice
  • N-Methylaspartate
  • Neurons / drug effects
  • Neurons / physiology*
  • Piperazines / pharmacology
  • Pyrrolidinones / pharmacology
  • Receptors, Glycine
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology*
  • Serine / antagonists & inhibitors
  • Serine / pharmacology*

Substances

  • Dibenzocycloheptenes
  • Piperazines
  • Pyrrolidinones
  • Receptors, Glycine
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • Aspartic Acid
  • Serine
  • N-Methylaspartate
  • Dizocilpine Maleate
  • Cycloserine
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • 1-hydroxy-3-amino-2-pyrrolidone
  • Cyclic GMP