Activation of protein kinase C by phorbol dibutyrate potentiates [³H]MK-801 binding in rat brain slices

Effects of activation of protein kinase C (PKC) on N-methyl-D-aspartate (NMDA) receptor function were analyzed by quantitative autoradiography using [³H]MK-801 in rat brain slices. The density of [³H]MK-801 binding was highest in hippocampus and high levels were found in cortex, striatum and thalamus. Levels in brainstem and molecular layer of cerebellum were low. The receptor binding was markedly deceased in almost all areas by addition of 2.5 mM Mg²⁺. After activation of PKC by 100 nM phorbol-12,13-dibutyrate (PDBu), [³H]MK-801 binding was increased in most areas, but binding levels were not changed in brainstem and cerebellum. The elevated [³H]MK-801 binding produced by PDBu was significantly inhibited by addition of Mg²⁺ except in inferior colliculus and cerebellum. These results suggest that activation of PKC potentiates NMDA receptor function in a region-specific manner in the rat brain.