Differential effects of phorbol myristate acetate and dexamethasone on protein kinase C activity and eicosanoids production in cultured rat astrocytes

The effects of phorbol myristate acetate (PMA) and dexamethasone on protein kinase C (PK‐C) activity and eicosanoid production were characterized in primary cultures of rat glial cells. PMA (1,000 ng/ml) treatment for 2 hr resulted in a maximal effect (a 4‐fold increase in PGE₂ production). Longer exposure to PMA (up to 96 hr) resulted in attenuation of PGE₂ production. Down‐regulation of PK‐C activity was assessed in glial cell homogenates under these conditions. Although a 70% inhibition of PK‐C activity was measured upon staurosporine treatment, PGE₂ production was not affected both under basal conditions and following PMA activation. The production of thromboxane B₂ did not change following exposure to PMA. Pretreatment of the cultures with dexamethasone markedly inhibited the PMA‐stimulated production of PGE₂ but had only a moderate (approximately 26%) inhibitory effect on PGE₂ production under basal conditions. Dexamethasone had no effect on basal or PMA‐stimulated PK‐C activity. Forskolin, which activates adenylate cyclase, did not affect PGE₂ production. These data may suggest that activation of PGE₂ production by PMA in glial cells is not unequivocally mediated by PK‐C activation. The inhibitory effect of dexamethasone on the PMA‐stimulated synthesis of PGE₂ supports previous findings that glucocorticoids are more effective in inhibiting stimulated rather than basal PGE₂ production. © 1993 Wiley‐Liss, Inc.