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Molecular Mechanisms of Drug Transporter Regulation

  • Rommel G. TironaEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 201)

Abstract

Interindividual differences in drug transporter expression can result in variability in drug response. This variation in gene expression is determined, in part, by the actions of nuclear hormone receptors that act as xenobiotic- and endobiotic-sensing transcription factors. Among the ligand-activated nuclear receptors, signaling through the Pregnane X Receptor (PXR), Constitutive Androstane Receptor (CAR), Farnesoid X Receptor (FXR), and Vitamin D Receptor (VDR) constitute major pathways regulating drug transporter expression in tissues. Hence, these endobiotic- and xenobiotic-sensing nuclear receptors are intrinsically involved in environmental influences of drug response. Moreover, because nuclear receptor genes are polymorphic, these transcription factors are also thought to contribute to heritability of variable drug action. In this chapter, the molecular aspects of drug transporter gene regulation by ligand-activated nuclear receptors will be reviewed including their clinical relevance.

Keywords

Gene expression Nuclear receptors Transcription factors Variable drug response 

Abbreviations

AhR

Aryl hydrocarbon receptor

BCRP

Breast cancer resistance protein

BSEP

Bile salt export pump

CAR

Constitutive androstane receptor

CYP

Cytochrome P450

FXR

Farnesoid X receptor

MATE1

Multidrug and toxin extrusion transporter member 1

MDR1

Multidrug resistance protein 1

MRP

Multidrug resistance-associated protein

Nrf2

Nuclear factor-E2-p45-related factor 2

NTCP

Sodium-taurocholate cotransporting polypeptide

OAT

Organic anion transporter

OATP

Organic anion transporting polypeptide

OCT

Organic cation transporter

OSTα/β

Organic solute transporter α/β

P-gp

P-glycoprotein

PPARγ

Peroxisome proliferator-activated receptor γ

PXR

Pregnane X receptor

RXR

9-cis retinoic acid receptor

SHP-1

Small heterodimer partner 1

SNP

Single nucleotide polymorphism

SULT

Sulfotransferase

UGT

UDP-glucuronosyltransferase

VDR

Vitamin D receptor

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© Springer Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Physiology and Pharmacology, Schulich School of Medicine and DentistryUniversity of Western Ontario, London Health Sciences Centre, University HospitalLondonCanada

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