Phenobarbital response element

Sueyoshi T, Negishi M Phenobarbital response elements of cytochrome P450 genes and nuclear receptors. Annu Rev Pharmacol Toxicol 2001 41 123. [PMID 11264453]... 

Trottier E, Belzil A, Stoltz C, Anderson A. Localization of a phenobarbital-responsive element (PBRE) in the 5 -flanking region of the rat CYP2B2 gene. Gene 1995 158 263-268. 

Constitutive Androstane Receptor (CAR) Activation Phenobarbital and phenytoin are known to induce metabolism of bilirubin, some bulky phenols, borneol, morphine, and steroidal UGTs catalyzed by UGTIAI, UGT1A9, and UGT2B7. Phenobarbital response elements (PBREMs) have been identified in these genes. 

Ethinyl estradiol, buprenorphine ferulic acid, genistein naltrexone (low), naloxone (low), SN-38 (active metabolite of irinotecan) alizarin, quinalizarin, retigabine Bilirubin, chloropheno- Atazanavir, indinavir, xypropionic acid, chrysin, ketoconazole (AT, = 3 pM) clofibrate, 3-MC, oltipraz, phenylpropionic acid, phenobarbital, clotrimazole, rifampin, and St. John s wort. WY-14643 Response elements for AhR, CAR, GR, PPAR-a, PXR, Nrf2 (antioxidant response element) have been identified... 

Figure 9.8. PB response elements in CYP102 and CYP2B genes. (From Kakizaki, S., Yamamoto, Y., Ueda, A., Moore, R., Sueyoshi, T., and Negishi, M. Phenobarbital induction of drug/steroid-metabolizing enzymes and nuclear receptor CAR. Biochim. Biophys. Acta 1619, 239-242, 2003.)...

Honkakoski, P., and Negishi, M. Regulatory DNA elements of phenobarbital-responsive cytochrome P450 CYP2B genes. /. Biochem. Molec. Toxicol. 12, 3,1998. 

However, the responsible xenobiotic response elements in the promoter region still remain to be elucidated. Note that the typical CAR ligands phenobarbital and TCPOBOP increase ligand binding and mRNA levels of AhR [173], suggesting complex NR cross talk. 

Y. Paquet, and A. Anderson (1998). The CYP2B2 phenobarbital response unit contains an accessory factor element and a putative glucocorticoid response element essential for conferring maximal phenobarbital responsiveness. J. Biol. Chem. 273, 8528-8536. 

The constitutive/active androstane receptor CAR, originally named MB67, was first cloned as a nuclear receptor that constitutively activates the retinoic acid response element in cell-based transfection assays [81], Then, from 1998 to 1999, the function of CAR relative to the induction of CRP genes as a phenobarbital activated nuclear receptor was established [7,82,83], Subsequently, the in vivo roles of CAR in induction were confirmed using CAR KO mice [84, 85], One of the major interests of the past half centuiy... 

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