TY - JOUR
T1 - Lack of modulation by phenobarbital of cyclic AMP levels or protein kinase A activity in rat primary hepatocytes
AU - Beck, Nancy B.
AU - Omiecinski, Curtis J.
N1 - Funding Information:
We gratefully acknowledge the excellent technical assistance of Dr. Fred Farin and Julia Tracy. We thank Dr. Jaspreet Sidhu for critical commentary. This research was supported by a grant from the National Institute of General Medical Sciences (GM32281). N. B. B. was supported by a National Institute of Environmental Health Sciences training grant (ES07032). C. J. O. is a Burroughs Wellcome Fund Toxicology Scholar.
PY - 1999/10/1
Y1 - 1999/10/1
N2 - 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. Copyright (C) 1999 Elsevier Science Inc.
AB - 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. Copyright (C) 1999 Elsevier Science Inc.
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U2 - 10.1016/S0006-2952(99)00189-6
DO - 10.1016/S0006-2952(99)00189-6
M3 - Article
C2 - 10484068
AN - SCOPUS:0033213808
SN - 0006-2952
VL - 58
SP - 1109
EP - 1114
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 7
ER -