TY - JOUR T1 - The Nuclear Receptors Constitutive Active/Androstane Receptor and Pregnane X Receptor Activate the <em>Cyp2c55</em> Gene in Mouse Liver JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1177 LP - 1182 DO - 10.1124/dmd.110.032334 VL - 38 IS - 7 AU - Yoshihiro Konno AU - Hiroki Kamino AU - Rick Moore AU - Fred Lih AU - Kenneth B. Tomer AU - Darryl C. Zeldin AU - Joyce A. Goldstein AU - Masahiko Negishi Y1 - 2010/07/01 UR - http://dmd.aspetjournals.org/content/38/7/1177.abstract N2 - Mouse CYP2C55 has been characterized as an enzyme that catalyzes synthesis of 19-hydroxyeicosatetraenoic acid (19-HETE), an arachidonic acid metabolite known to have important physiological functions such as regulation of renal vascular tone and ion transport. We have now found that CYP2C55 is induced by phenobarbital (PB) and pregnenolone 16α-carbonitrile (PCN) in both mouse kidney and liver. The nuclear xenobiotic receptors constitutive active/androstane receptor (CAR) and pregnane X receptor (PXR) regulate these drug inductions: CYP2C55 mRNA was increased 25-fold in PB-treated Car(+/+) but not in Car(−/−) mice and was induced in Pxr(+/+) but not Pxr(−/−) mice after PCN treatment. Cell-based promoter analysis and gel shift assays identified the DNA sequence −1679TGAACCCAGTTGAACT−1664 as a DR4 motif that regulates CAR- and PXR-mediated transcription of the Cyp2c55 gene. Chronic PB treatment increased hepatic microsomal CYP2C55 protein and serum 19-HETE levels. These findings indicate that CAR and PXR may play a role in regulation of drug-induced synthesis of 19-HETE in the mouse. U.S. Government work not protected by U.S. copyright ER -