Glycine, glycinamide and d-serine act as positive modulators of signal transduction at the N-Methyl-D-Aspartate (NMDA) receptor in vivo: Differential effects on mouse cerebellar cyclic guanosine monophosphate levels

T. S. Rao, Julie A. Cler, M. R. Emmett, S. J. Mick, S. Iyengar, P. L. Wood

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Direct intracerebellar (icb) administration of glycine, glycinamide and D-serine produced time- and dose-dependent changes in mouse cerebellar cGMP levels, indicating a modulation of ongoing neuronal activity through the NMDA receptor complex. Intracerebro-ventricular administration of glycinamide also produced a timedependent change in cGMP levels, indicating a central mechanism of action. The icb dose-response data indicated a unimolecular interaction for these compounds. D-serine-, glycine-, and glycinamide-mediated increases in cGMP levels were reversed by the competitive NMDA antagonist, CPP and the NMDA-associated glycine receptor antagonist, HA-966, indicating mediation via the NMDA receptor complex. Glycine and D-serine were less effective than glycinamide at increasing cerebellar cGMP levels. In contrast, L-and D-serinamide did not affect cGMP levels. These results indicate that glycine receptor is not saturated under physiological conditions and also suggest possible existence of multiple glycine pools.

Original languageEnglish (US)
Pages (from-to)1075-1080
Number of pages6
JournalNeuropharmacology
Volume29
Issue number11
DOIs
StatePublished - Nov 1990
Externally publishedYes

Keywords

  • D-serine
  • cyclic GMP
  • glycinamide
  • glycine

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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