Drug-activated nuclear receptors CAR and PXR

被引：142
|
作者：
Honkakoski, P
Sueyoshi, T
Negishi, M
机构：
[1] NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA
[2] Univ Kuopio, Dept Pharmaceut, FIN-70211 Kuopio, Finland
来源：
ANNALS OF MEDICINE | 2003年 / 35卷 / 03期
关键词：
CAR; cytochrome P450; drug metabolism; induction; intestine; liver; nuclear receptor; PXR; RXR;
D O I：
10.1080/07853890310008224
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
The metabolism and elimination of drugs is mainly mediated by cytochrome P450 (CYP) enzymes, aided by conjugative enzymes and transport proteins. An integral aspect of this elimination process is the induction of drug metabolism through activation of gene expression of metabolic and transport proteins. There is compelling evidence that induction is regulated by drug-activated nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR). This review outlines the basic properties of CAR and PXR, their ligands and target genes, and the mechanisms of the induction process. The implications of nuclear receptor-mediated induction for drug research are also discussed.
引用
收藏
页码：172 / 182
页数：11
相关论文
共 50 条
  • [21] Reciprocal activation of Xenobiotic response genes by nuclear receptors SXR/PXR and CAR
    Xie, W
    Barwick, JL
    Simon, CM
    Pierce, AM
    Safe, S
    Blumberg, B
    Guzelian, PS
    Evans, RM
    GENES & DEVELOPMENT, 2000, 14 (23) : 3014 - 3023
  • [22] Specific and overlapping functions of the nuclear hormone receptors CAR and PXR in xenobiotic response
    Wei P.
    Zhang J.
    Dowhan D.H.
    Han Y.
    Moore D.D.
    The Pharmacogenomics Journal, 2002, 2 (2) : 117 - 126
  • [23] Ligand Dependent Hepatic Gene Expression Profiles of Nuclear Receptors Car and PXR
    Kakizaki, Satoru
    Tojima, Hiroki
    Yamazaki, Yuichi
    Takizawa, Daichi
    Horiguchi, Norio
    Sohara, Naondo
    Sato, Ken
    Mori, Masatomo
    GASTROENTEROLOGY, 2012, 142 (05) : S988 - S988
  • [24] Ligand dependent hepatic gene expression profiles of nuclear receptors CAR and PXR
    Tojima, Hiroki
    Kakizaki, Satoru
    Yamazaki, Yuichi
    Takizawa, Daichi
    Horiguchi, Norio
    Sato, Ken
    Mori, Masatomo
    TOXICOLOGY LETTERS, 2012, 212 (03) : 288 - 297
  • [25] Impact of Nuclear Receptors CAR, PXR, FXR, and VDR, and Their Ligands On Enzymes and Transporters
    Tirona, Rommel G.
    ENZYME- AND TRANSPORTER-BASED DRUG-DRUG INTERACTIONS: PROGRESS AND FUTURE CHALLENGES, 2010, : 75 - 105
  • [26] Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate drug-metabolizing and gluconeogenic enzymes
    Kodama, S
    Koike, C
    Yamamoto, Y
    Negishi, M
    DRUG METABOLISM REVIEWS, 2004, 36 : 311 - 311
  • [27] The nuclear receptors CAR and PXR control induction of cytochromes P450 by phenobarbital
    Corcos, C
    Brey, J
    Corcos, L
    M S-MEDECINE SCIENCES, 2002, 18 (04): : 429 - 437
  • [28] CAR and PXR: The xenobiotic-sensing receptors
    Timsit, Yoav E.
    Negishi, Masahiko
    STEROIDS, 2007, 72 (03) : 231 - 246
  • [29] Binding of Drug-Activated CAR/Nr1i3 Alters Metabolic Regulation in the Liver
    Tian, Jianmin
    Marino, Rebecca
    Johnson, Carla
    Locker, Joseph
    ISCIENCE, 2018, 9 : 209 - +
  • [30] Role of Nuclear Receptors PXR and CAR in Xenobiotic-Induced Hepatocyte Proliferation and Chemical Carcinogenesis
    Yoshinari, Kouichi
    BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2019, 42 (08) : 1243 - 1252
12345