Lack of modulation by phenobarbital of cyclic AMP levels or protein kinase A activity in rat primary hepatocytes.
Results of previous studies have substantiated a negative modulatory role for 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 pathways in the initial phases of induction, specifically addressing the effects of PB on the expression of intracellular cAMP levels and associated PKA activity. Using a highly differentiated primary rat hepatocyte system, cells were exposed to PB for various intervals (30 sec to 48 hr), and levels of intracellular cAMP and subsequent PKA activity were determined. Although PB markedly induced CYP2B expression, exposure to this agent produced no detectable increases in cAMP levels and PKA activity at any of the times examined. These results demonstrated that the initial events stimulated by PB in rat hepatocytes do not include alterations of cAMP levels or associated PKA activities.
Beck
N B
NB
Department of Environmental Health, University of Washington, Seattle 98105-6099, USA.
Omiecinski
C J
CJ
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D003577:Cytochrome P-450 Enzyme System; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010634:Phenobarbital