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Title: The Ah Receptor: Adaptive Metabolism, Ligand Diversity, and the Xenokine Model.

Authors: Avilla, Mele N; Malecki, Kristen M C; Hahn, Mark E; Wilson, Rachel H; Bradfield, Christopher A

Published In Chem Res Toxicol, (2020 Apr 20)

Abstract: The Ah receptor (AHR) has been studied for almost five decades. Yet, we still have many important questions about its role in normal physiology and development. Moreover, we still do not fully understand how this protein mediates the adverse effects of a variety of environmental pollutants, such as the polycyclic aromatic hydrocarbons (PAHs), the chlorinated dibenzo-p-dioxins ("dioxins"), and many polyhalogenated biphenyls. To provide a platform for future research, we provide the historical underpinnings of our current state of knowledge about AHR signal transduction, identify a few areas of needed research, and then develop concepts such as adaptive metabolism, ligand structural diversity, and the importance of proligands in receptor activation. We finish with a discussion of the cognate physiological role of the AHR, our perspective on why this receptor is so highly conserved, and how we might think about its cognate ligands in the future.

PubMed ID: 32259433 Exiting the NIEHS site

MeSH Terms: Animals; Environmental Pollutants/chemistry; Environmental Pollutants/pharmacology*; Humans; Ligands; Molecular Structure; Polychlorinated Dibenzodioxins/chemistry; Polychlorinated Dibenzodioxins/pharmacology*; Polycyclic Aromatic Hydrocarbons/chemistry; Polycyclic Aromatic Hydrocarbons/pharmacology*; Receptors, Aryl Hydrocarbon/genetics; Receptors, Aryl Hydrocarbon/metabolism*; Signal Transduction/drug effects

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