INTERACTION OF PROTEIN KINASE-A AND KINASE-C IN THEIR EFFECTS ON THE PROENKEPHALIN GENE IN ASTROGLIAL CELLS

In several cell types, the expression of the proenkephalin (PEnk) gene is enhanced after activation of protein kinase A. In the present stud y, astroglial cells cultured from rat cortex were used to investigate whether protein kinases A and C can act in a synergistic manner on the endogenous proenkephalin gene The activator of protein kinase C tetra decanoylphorbolacetate (0.001-1 mu M) increased the level of proenkeph alin-mRNA in a concentration dependent manner. When used together with the phosphodiesterase inhibitor Rolipram (1 mu M), the effect of tetr adecanoylphorbolacetate (0.01 mu M) was potentiated. 8-Bromoadenosine 3',5'-cyclic monophosphate (0.01-1 mM) also enhanced the expression of the proenkephalin gene. When used together with tetradecanoylphorbola cetale (0.01 and 0.1 mu M), respectively, both agents had additive eff ects. Inhibition of protein synthesis with cycloheximide (35 mu M) sig nificantly changed the effects of both agents. While the effect of 8Br .cAMP (1 mM) on PEnk-mRNA was enhanced, that of tetradecanoylphorbolac etate (0.1 mu M) was abolished. The results provide evidence for a syn ergistic effect of protein kinase A and C on the expression of the pro enkephalin gene in astroglial cells. However, the protein kinases seem to act via different transcription factors on the expression of the p roenkephalin gene.