EFFECT OF PROTEIN-KINASE-C ACTIVATION ON N-METHYL-D-ASPARTATE-EVOKED RELEASE OF ADENOSINE AND [H-3]NOREPINEPHRINE FROM RAT CORTICAL SLICES

The role of protein kinase C (PKC) in the N-methyl-D-aspartate (NMDA)- evoked release of adenosine (ADO) and [H-3]norepinephrine (NE) from sl ices of rat parietal cortex was studied. In the absence of Mg++, the P KC activator phorbol 12-myristate 13-acetate (1 mu M, PMA) did not rel ease either ADO or [H-3]NE, but it potentiated the release of ADO evok ed by 20 mu M NMDA and the release of [H-3]NE evoked by 100 mu M NMDA. These potentiating effects of PMA on the NMDA-evoked release of ADO a nd [H-3]NE were reversed by the PKC inhibitor GF109,203X(1 mu M). GF10 9,203X by itself had no effect on the NMDA-evoked release of either AD O or [H-3]NE. In the presence of Mg++, PMA did not permit the NMDA-evo ked release of [H-3]NE to occur. These results indicate that PKC does not play an essential role in the NMDA-evoked release of either ADO or NE. However, activation of PKC potentiates the release of ADO and NE evoked by submaximal concentrations of NMDA. Activation of PKC will ha ve the effect of increasing the inhibitory threshold provided by relea sed ADO when only a few NMDA receptors are activated and will promote and accelerate excitatory responses when most of the available NMDA re ceptors become activated.