NMDA INDUCES PROTEIN-KINASE-C TRANSLOCATION IN GUINEA-PIG CEREBRAL SYNAPTONEUROSOMES

N-methyl-D-aspartate (NMDA)-induced translocation of protein kinase C from the cytosol to membrane fractions was examined by the [H-3]phorbol 12,13-dibutyrate (PDBu) binding method in guinea pig cerebral synaptoneurosomes. Pretreatment of synaptoneurosomes with NMDA, but not that with quisqualate or kainate, induced changes in the distribution of [H-3]PDBu binding in the cytosol and membrane fractions in a dose-dependent manner. The NMDA-induced changes of the binding were completely dependent on Ca2+ and inhibited by NMDA receptor antagonists Mg2+, 2-amino-5-phosphonovaleric acid and ketamine, but not by Zn2+. Glycine slightly potentiated the NMDA-induced changes of [H-3]PDBu binding. NMDA stimulated Ca2+ uptake but not the phosphoinositide hydrolysis in the synaptoneurosomes. These results suggest that NMDA enhances Ca2+ influx through receptor-operated Ca2+ channels, increasing intracellular calcium concentration and thereby induces translocation of protein kinase C.