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 signal inside the cell (increased ions, second messengers, phosphorylation of substrate, see Figure 1). A common feature of the xenobiotic ligands of these receptors is that they are lipophilic compounds that can diffuse across the cell membrane with moderate ease. The interaction with the xenobiotic receptor may occur predominantly in the cytosol (AhR) or in the nucleus (ER, PXR). The ability of xenobiotic receptors to regulate gene expression makes them potent regulators of the cell cycle and apoptosis. In addition, many cytochrome P450 enzymes are regulated by xenobiotic receptors. In addition to affecting the metabolism of endogenous compounds, enzyme induction is an important aspect of drug-drug interactions and toxicity.
Date of publication: 2015
Author: Jack Vanden Heuvel, PhD; INDIGO Biosciences, Inc.