title: Cyclic AMP-independent activation of CYP3A4 gene expression by forskolin.
abstract: Forskolin and cAMP have been shown to have paradoxical effects in the regulation of expression levels of mRNA of cytochrome P450 3A (CYP3A) family members. We demonstrate in this study that forskolin upregulated the promoter for CYP3A4 independent of its ability to increase cAMP levels. This activity was explained showing forskolin directly activated the pregnane-X-receptor, a known regulator of CYP3A genes.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Co., 20 T.W. Alexander Drive, P.O. Box 13951, Research Triangle Park, NC 27709-3951, USA.
authors.forename: Michele S
authors.initials: MS
authors.lastname: Dowless
authors.forename: James L
authors.initials: JL
authors.lastname: Barbee
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Borchert
authors.forename: Wayne P
authors.initials: WP
authors.lastname: Bocchinfuso
authors.forename: Keith A
authors.initials: KA
authors.lastname: Houck
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004789:Enzyme Activation; D051548:Histone Acetyltransferases; D006801:Humans; D008024:Ligands; D056920:Nuclear Receptor Coactivator 1; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D008024:Ligands; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003577:Cytochrome P-450 Enzyme System; D000242:Cyclic AMP; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1