PT - JOURNAL ARTICLE AU - Gary H. Perdew AU - Iain A. Murray AU - Troy D. Hubbard TI - Indole and tryptophan metabolism: endogenous and dietary routes to Ah receptor activation AID - 10.1124/dmd.115.064246 DP - 2015 Jan 01 TA - Drug Metabolism and Disposition PG - dmd.115.064246 4099 - http://dmd.aspetjournals.org/content/early/2015/06/02/dmd.115.064246.short 4100 - http://dmd.aspetjournals.org/content/early/2015/06/02/dmd.115.064246.full AB - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor recognized for its role in xenobiotic metabolism. The physiological function of the AHR has expanded to include roles in immune regulation, organogenesis, mucosal barrier function, and cell cycle. These functions are likely dependent upon ligand-mediated activation of the receptor. High affinity ligands of the AHR have been classically defined as xenobiotics, such as polychlorinated biphenyls and dioxins. Identification of endogenous AHR ligands is key to understanding the physiological functions of this enigmatic receptor. Metabolic pathways targeting the amino acid tryptophan and indole can lead to a myriad of metabolites, some of which are AHR ligands. Many of these ligands exhibit species selective preferential binding to the AHR. The discovery of specific tryptophan metabolites as AHR ligands may provide insight concerning where the AHR is activated in an organism, such as at the site of inflammation and within the intestinal tract.