NMDA Induces Protein Kinase C Translocation in Guinea Pig Cerebral Synaptoneurosomes

Abstract

N-methyl-D-aspartate (NMDA)-induced translocation of protein kinase C from the cytosol to membrane fractions was examined by the [³H]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 [³H]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 [³H]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.