Molecular Mechanisms of Drug Transporter Regulation

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


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.


Gene expression Nuclear receptors Transcription factors Variable drug response 



Aryl hydrocarbon receptor


Breast cancer resistance protein


Bile salt export pump


Constitutive androstane receptor


Cytochrome P450


Farnesoid X receptor


Multidrug and toxin extrusion transporter member 1


Multidrug resistance protein 1


Multidrug resistance-associated protein


Nuclear factor-E2-p45-related factor 2


Sodium-taurocholate cotransporting polypeptide


Organic anion transporter


Organic anion transporting polypeptide


Organic cation transporter


Organic solute transporter α/β




Peroxisome proliferator-activated receptor γ


Pregnane X receptor


9-cis retinoic acid receptor


Small heterodimer partner 1


Single nucleotide polymorphism






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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