Glycine and D-serine act as positive modulators of signal transduction at N-methyl-D-aspartate sensitive glutamate receptors in cultured cerebellar granule cells

• Published in: Neuropharmacology Vol. 28; no. 5; p. 447
• Main Authors: Wroblewski, J T, Fadda, E, Mazzetta, J, Lazarewicz, J W, Costa, E
• Format: Journal Article
• Language: English
• Published: England 01.05.1989
• Subjects: Animals; Aspartic Acid - analogs & derivatives; Aspartic Acid - pharmacology; Calcium - metabolism; Calcium Radioisotopes; Cells, Cultured; Cerebellum - cytology; Cerebellum - drug effects; Cerebellum - physiology; Glycine - pharmacology; N-Methylaspartate; Phencyclidine - pharmacology; Rats; Rats, Inbred Strains; Receptors, Glutamate; Receptors, Neurotransmitter - physiology; Serine - pharmacology; Signal Transduction - drug effects; Strychnine - pharmacology
• ISSN: 0028-3908
• DOI: 10.1016/0028-3908(89)90077-4

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.