Phenobarbital confers its diverse effects by activating the orphan nuclear receptor CAR

Susumu Kodama, Masahiko Negishi

Research output: Contribution to journalReview article

61 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)75-87
Number of pages13
JournalDrug Metabolism Reviews
Volume38
Issue number1-2
DOIs
Publication statusPublished - 2006
Externally publishedYes

Fingerprint

Phenobarbital
Liver
Drug Tolerance
Bile Acids and Salts
Thyroid Hormones
Cell Communication
Endoplasmic Reticulum
Pharmaceutical Preparations
Steroids
Glucose
constitutive androstane receptor
Growth
Genes
Neoplasms

Keywords

  • CAR
  • Cytochrome P450
  • Gene transcription
  • Gluconeogenesis
  • Hepatic metabolism
  • Hepatocellular carcinoma
  • Liver
  • Nuclear receptors

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Phenobarbital confers its diverse effects by activating the orphan nuclear receptor CAR. / Kodama, Susumu; Negishi, Masahiko.

In: Drug Metabolism Reviews, Vol. 38, No. 1-2, 2006, p. 75-87.

Research output: Contribution to journalReview article

@article{4b3ec55469814cc299ab71a521353f62,
title = "Phenobarbital confers its diverse effects by activating the orphan nuclear receptor CAR",
abstract = "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.",
keywords = "CAR, Cytochrome P450, Gene transcription, Gluconeogenesis, Hepatic metabolism, Hepatocellular carcinoma, Liver, Nuclear receptors",
author = "Susumu Kodama and Masahiko Negishi",
year = "2006",
doi = "10.1080/03602530600569851",
language = "English",
volume = "38",
pages = "75--87",
journal = "Drug Metabolism Reviews",
issn = "0360-2532",
publisher = "Informa Healthcare",
number = "1-2",

}

TY - JOUR

T1 - Phenobarbital confers its diverse effects by activating the orphan nuclear receptor CAR

AU - Kodama, Susumu

AU - Negishi, Masahiko

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

KW - CAR

KW - Cytochrome P450

KW - Gene transcription

KW - Gluconeogenesis

KW - Hepatic metabolism

KW - Hepatocellular carcinoma

KW - Liver

KW - Nuclear receptors

UR - http://www.scopus.com/inward/record.url?scp=33646713469&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646713469&partnerID=8YFLogxK

U2 - 10.1080/03602530600569851

DO - 10.1080/03602530600569851

M3 - Review article

VL - 38

SP - 75

EP - 87

JO - Drug Metabolism Reviews

JF - Drug Metabolism Reviews

SN - 0360-2532

IS - 1-2

ER -