PT  - JOURNAL ARTICLE
AU  - Konno, Yoshihiro
AU  - Kamino, Hiroki
AU  - Moore, Rick
AU  - Lih, Fred
AU  - Tomer, Kenneth B.
AU  - Zeldin, Darryl C.
AU  - Goldstein, Joyce A.
AU  - Negishi, Masahiko
TI  - The Nuclear Receptors Constitutive Active/Androstane Receptor and Pregnane X Receptor Activate the <em>Cyp2c55</em> Gene in Mouse Liver
AID  - 10.1124/dmd.110.032334
DP  - 2010 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 1177--1182
VI  - 38
IP  - 7
4099  - http://dmd.aspetjournals.org/content/38/7/1177.short
4100  - http://dmd.aspetjournals.org/content/38/7/1177.full
SO  - Drug Metab Dispos2010 Jul 01; 38
AB  - 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