Chapter 7 - Receptors and drug-metabolizing enzymes: From function to regulation

Abstract

Drug-metabolizing enzymes (DMEs) and receptors have a significant role in the detoxification and disposal of endogenous chemical substances. The receptor system is involved in the cellular input/output of chemicals and medicines. DME regulates the expression of DME genes through the activation of a number of nuclear receptors (NRs) by a variety of endogenous and foreign substances that are DME substrates. Different regulatory regions located in the promoter region of the DME genes are directly or indirectly targeted by these NRs in order to respond chemical demands, transcription of several DMEs and NRs, and ligand-activated factors and transporters (NRs). The most promising xenobiotic receptors, such as pregnane X receptor (PXR), constitutive androstane/activator receptor (CAR), and aryl hydrocarbon receptors, are all examples of NRs in xenobiotic metabolism (AHR). These receptors together regulate the expression of substantially overlapping array of biotransformation on DME target genes and drug receptors. Recognizing the impact of xenobiotic receptors on metabolism of drugs will help to enhance the safe use of drugs and establish new therapeutic strategies based on xenobiotic receptors. In this chapter, PXR and CAR as xenosensors, their processes, interactions to elucidate the cross talk between them in regulation of DMEs are discussed.