PMID- 10415106
OWN - NLM
STAT- MEDLINE
DCOM- 19990908
LR  - 20181201
IS  - 0003-9861 (Print)
IS  - 0003-9861 (Linking)
VI  - 368
IP  - 1
DP  - 1999 Aug 1
TI  - Rat pregnane X receptor: molecular cloning, tissue distribution, and xenobiotic
      regulation.
PG  - 14-22
AB  - An orphan nuclear receptor, termed the pregnane X receptor (PXR), has recently
      been cloned from mouse and human and defines a novel steroid signaling pathway
      (Cell 92, 73-82, 1998; Proc. Natl. Acad. Sci. USA 95, 12208-122313, 1998).
      Transient cotransfection experiments demonstrate that the PXR responds to
      structurally dissimilar compounds and confers the induction of cytochrome P4503A 
      (CYP3A), a subfamily of enzymes that involve the metabolism of two-thirds of
      drugs and other xenobiotics. In this report, we describe the molecular cloning,
      tissue distribution, and xenobiotic regulation of a rat PXR designated rPXR-1.
      rPXR-1 exhibits a 95% sequence identity with the mouse PXR, but only 79% identity
      with the human PXR, providing the molecular basis that rats and mice have a
      similar CYP3A induction profile but differ from humans. rPXR-1 gene was expressed
      abundantly in liver, intestine, and, to a lesser extent, kidney, lung, and
      stomach. The tissue distribution and the relative abundance of rPXR-1 mRNA among 
      these tissues resemble those of CYP3A, suggesting that PXR is important not only 
      for induction but also for constitutive expression of these enzymes. Xenobiotics 
      known to induce liver microsomal enzymes showed differential effects on the
      rPXR-1 expression as determined by Northern blot analysis. Dexamethasone, for
      example, increased the accumulation of rPXR-1 mRNA, whereas troleandomycin
      slightly suppressed it. Compounds that increase PXR expression (inducers) and
      compounds that interact with PXR (ligands) likely have synergistic effects on
      CYP3A induction, which provides a novel molecular explanation for drug-drug
      interactions.
CI  - Copyright 1999 Academic Press.
FAU - Zhang, H
AU  - Zhang H
AD  - Department of Biomedical Sciences, University of Rhode Island, Kingston, Rhode
      Island, 02881, USA.
FAU - LeCulyse, E
AU  - LeCulyse E
FAU - Liu, L
AU  - Liu L
FAU - Hu, M
AU  - Hu M
FAU - Matoney, L
AU  - Matoney L
FAU - Zhu, W
AU  - Zhu W
FAU - Yan, B
AU  - Yan B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (DNA, Complementary)
RN  - 0 (Pregnane X Receptor)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Xenobiotics)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - EC 1.5.- (Oxidoreductases, N-Demethylating)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Aryl Hydrocarbon Hydroxylases
MH  - Base Sequence
MH  - Cloning, Molecular
MH  - Cytochrome P-450 CYP3A
MH  - Cytochrome P-450 Enzyme System/biosynthesis
MH  - DNA, Complementary/genetics
MH  - Enzyme Induction
MH  - Female
MH  - Humans
MH  - Male
MH  - Mice
MH  - Molecular Sequence Data
MH  - Oxidoreductases, N-Demethylating/biosynthesis
MH  - Pregnane X Receptor
MH  - Protein Biosynthesis
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Cytoplasmic and Nuclear/drug effects/*genetics/*metabolism
MH  - Receptors, Steroid/drug effects/*genetics/*metabolism
MH  - Sequence Homology, Amino Acid
MH  - Tissue Distribution
MH  - Transcription, Genetic
MH  - Xenobiotics/metabolism/pharmacology
EDAT- 1999/07/23 00:00
MHDA- 1999/07/23 00:01
CRDT- 1999/07/23 00:00
PHST- 1999/07/23 00:00 [pubmed]
PHST- 1999/07/23 00:01 [medline]
PHST- 1999/07/23 00:00 [entrez]
AID - 10.1006/abbi.1999.1307 [doi]
AID - S0003-9861(99)91307-3 [pii]
PST - ppublish
SO  - Arch Biochem Biophys. 1999 Aug 1;368(1):14-22. doi: 10.1006/abbi.1999.1307.