Lack of modulation by phenobarbital of cyclic AMP levels or protein kinasea activity in rat primary hepatocytes

Results of previous studies have substantiated a negative modulatory role f or cyclic AMP (cAMP) and protein kinase A (PKA) dependent processes on the phenobarbital (PB) induction response in hepatocytes. The current study was conducted to further examine the potential role of second messenger pathwa ys in the initial phases of induction, specifically addressing the effects of PB on the expression of intracellular cAMP levels and associated PKA act ivity. Using a highly differentiated primary rat hepatocyte system, cells w ere exposed to PB for various intervals (30 sec to 48 hr), and levels of in tracellular cAMP and subsequent PKA activity were determined. Although PB m arkedly induced CYP2B expression, exposure to this agent produced no detect able increases in cAMP levels and PKA activity at any of the times examined . These results demonstrated that the initial events stimulated by PB in ra t hepatocytes do not include alterations of cAMP levels or associated PKA a ctivities. (C) 1999 Elsevier Science Inc.