INTRODUCTION Nuclear Receptors act as transcription factors that mediate the effects of certain hormones, drugs, and other xenobiotics by modulating the expression of specific genes involved in many cellular functions such as development, reproduction, and metabolism. Conserved functional domains of nuclear receptors such as the DNA-binding domain (DBD), ligand-binding domain (LBD), N- and C-terminal transcriptionalRead More
Xenobiotic, Bile Acid, and Cholesterol Transporters
INTRODUCTION Uptake and efflux transporters determine plasma and tissue concentrations of a broad variety of drugs, nutrients, and xenobiotics (1-3). The liver is the primary organ for the metabolic degradation of xenobiotics. Transmembrane transport proteins from the ATP binding cassette (ABC) and the solute carrier (SLC) families mediate the uptake and efflux of endogenous compounds,Read More
Species Differences in Pregnane X Receptor Activation: Examination of common laboratory animal species
INTRODUCTION Nuclear receptors (NRs) are ligand-dependent transcription factors found in many species that regulate the expression of important target genes involved in a spectrum of developmental and physiological processes. In addition to ligand binding, the transcriptional activities of NRs are also modulated through a range of protein-protein interactions with coregulatory proteins, either with coactivator orRead More
Drug-Nutrient Interactions and Nuclear Receptors
INTRODUCTION There are several clinically relevant instances of a food or dietary supplement altering the activity of a pharmaceutical agent. For example, St. John’s Wort (Hypericum perforatum), a popular herbal antidepressant, affects pharmacokinetic actions of HIV protease inhibitors, antidepressants, antihypertensives, and oral contraceptives. Drug-nutrient interaction (DNI) represents a relationship between a medication and one orRead More
Gene Expression: Nuclear Receptors
INTRODUCTION There are four main classes of receptors, Ion channels, G-protein coupled (GPCR), receptor tyrosine kinase and soluble (also called intracellular) receptors. The first three have ligands that are mainly present in the extracellular space (water soluble ligands). The binding of ligand causes a change in the shape/function of the protein that generates a signalRead More
Nuclear Receptors & Endocrine / Metabolic Disruption
INTRODUCTION There are many important environmental chemicals that are of concern due to their ability to affect the endocrine system, so-called endocrine disrupting chemicals (EDCs). Compounds that cause endocrine disruption may do so by altering drug and xenobiotic metabolic processes; hence, a subgroup of EDCs may also be considered “metabolic disruptors” as well. In thisRead More