Glycine and D-serine act as positive modulators of signal transduction at N-methyl-D-aspartate sensitive glutamate receptors in cultured cerebellar granule cells.
In cultures of rat neonatal cerebellar granule cells the signal transduction at ionotropic NMDA-sensitive glutamate receptors (GC1) was measured as an increase of influx of 45Ca2+. This transmitter-mediated influx of Ca2+ was enhanced by glycine and D-serine in a dose-dependent manner. D-Alanine was less active than glycine and D-serine, while L-alanine and L-serine were inactive. These amino acids failed to activate basal influx of Ca2+. Activation of calcium influx at GC2 receptors by kainate was unchanged by the amino acids mentioned above. Glycine and D-serine increased the potency but failed to change the efficacy of GC1 agonists. This action was not changed by strychnine. The enhancement of aspartate signal transduction by glycine and D-serine was inhibited by the noncompetitive GC1 receptor antagonist, phencyclidine, but was even more evident in presence of Mg2+ ions. Hence, glycine and D-serine may function as positive allosteric modulators of signal transduction at NMDA-sensitive (GC1) glutamate receptors.
Wroblewski
J T
JT
Fidia-Georgetown Institute for the Neurosciences, Georgetown University School of Medicine, Washington, D.C. 20007.
Fadda
E
E
Mazzetta
J
J
Lazarewicz
J W
JW
Costa
E
E
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005998:Glycine / Q000494:pharmacology*; D016202:N-Methylaspartate; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D012694:Serine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013331:Strychnine / Q000494:pharmacology
D002132:Calcium Radioisotopes; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D012694:Serine; D016202:N-Methylaspartate; D013331:Strychnine; D010622:Phencyclidine; D002118:Calcium; D005998:Glycine