Kodama Susumu, Negishi Masahiko
Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Drug Metab Rev. 2006;38(1-2):75-87. doi: 10.1080/03602530600569851.
In the early 1960s, phenobarbital (PB) was shown to induce hepatic drug metabolism and the induction was implicated in the molecular mechanism of drug tolerance development. Since then, it has become evident that PB not only induces drug metabolism, but also triggers pleiotropic effects on liver function, such as cell growth and communication, proliferation of the endoplasmic reticulum, tumor promotion, glucose metabolism, steroid/thyroid hormone metabolism, and bile acid synthesis. Upon activation by PB and numerous PB-type inducers, the nuclear receptor CAR mediates those pleiotropic actions by regulating various hepatic genes, utilizing multiple regulatory mechanisms.
20世纪60年代初，苯巴比妥（PB）被证明可诱导肝脏药物代谢，且这种诱导作用与药物耐受性产生的分子机制有关。从那时起，很明显PB不仅诱导药物代谢，还会引发对肝功能的多效性影响，如细胞生长与通讯、内质网增殖、肿瘤促进、葡萄糖代谢、类固醇/甲状腺激素代谢以及胆汁酸合成。在被PB和众多PB型诱导剂激活后，核受体CAR通过利用多种调控机制调节各种肝脏基因，介导这些多效性作用。
