Regulation of phenobarbital-induction of CYP2B and CYP3A genes in rat cultured hepatocytes: involvement of several serine/threonine protein kinases and phosphatases.

摘要: We investigated the involvement of diverse protein kinases and phosphatases in transduction pathways elicited by phenobarbital (PB), a well-known inducer some hepatic cytochromes P450 (CYP). Different inhibitors or activators were assessed for their ability to modulate PB-induction CYP2B CYP3A mRNA expression. Rat hepatocytes primary culture treated with test compounds one hour prior to, then continuously, absence presence 1 mmol/L PB 24 h. By northern blot analysis CYP2B1/2 3A1/2 gene expression, we first confirmed negative role adenosine 3′:5′ cyclic monophosphate (cAMP)/protein kinase A pathway positive serine/threonine mechanism PB-induction. The present data further suggested that Ca2+/calmodulin-dependent II (independently Ca2+) extracellular signal-regulated 1/2 (ERK1/2) might function respectively as regulator CYP3A. In contrast, C phosphatidylinositol-3-kinase did not appear be involved, while tyrosine remained unclear. conclude complex network phosphorylation/dephosphorylation events crucial rat