Administration of dexamethasone up-regulates protein kinase C activity andthe expression of gamma and epsilon protein kinase C isozymes in the rat brain

Altered hypothalamic-pituitary-adrenal (HPA) function (increased plasma coi tisol level) has been shown to be associated with mood and behavior. Protei n kinase C (PKC), an important component of the phosphatidylinositol signal transduction system, plays a major role in mediating various physiological functions. The present study investigates the effects of acute (single) an d repeated (10-day) administrations of 0.5 or 1.0 mg/kg doses of dexamethas one (DEX), a synthetic glucocorticoid, on B-max and K-D of [H-3]phorbol 12, 13-dibutyrate ([H-3]PDBu) binding, PKC activity, and protein expression of PKC isozymes alpha, beta, gamma, delta, and epsilon in the membrane and the cytosolic fractions of rat cortex and hippocampus. It was observed that re peated administration of 1.0 mg/kg DEX for 10 days caused a significant inc rease in B-max of [H-3]PDBu binding to PKC, in PKC activity, and in express ed protein levels of the gamma and epsilon isozymes in both the cytosolic a nd the membrane fractions of the cortex and the hippocampus, whereas a lowe r dose of DEX (0.5 mg/kg for 10 days) caused these changes only in the hipp ocampus. On the other hand, a single administration of DEX (0.5 or 1.0 mg/k g) had no significant effect on PKC in the cortex or in the hippocampus. Th ese results suggest that alterations in HPA function from repeated administ ration of glucocorticoids may modulate PKC-mediated functions.