Tryptophan metabolites exhibit aryl hydrocarbon receptor (AhR) agonist activity and recent studies show that the phenylalanine metabolites serotonin and carbidopa, a drug used in treating Parkinson's disease, activated the AhR. In this study, we identified the neuroactive hormone dopamine as an inducer of drug-metabolizing enzymes CYP1A1, CYP1B1, and UGT1A1 in colon and glioblastoma cells and similar results were observed for carbidopa. In contrast, carbidopa but not dopamine exhibited AhR activity in BxPC3 pancreatic cancer cells whereas minimal activity was observed for both compounds in Panc1 pancreatic cancer cells. In contrast with a previous report, the induction responses and cytotoxicity of carbidopa was observed only at high concentrations (100 µM) in BxPC3 cells. Our results show that similar to serotonin and several tryptophan metabolites, dopamine is also an AhR-active compound.
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October 2020
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The cover image showing the crystal structure of human hemoglobin (PDB: 1GZX). For more information, see the article by Natarajan et al. (pp. 3839–3850). Artwork Image courtesy of C. Natarajan.
Research Article|
October 16 2020
Dopamine is an aryl hydrocarbon receptor agonist
Hyejin Park;
Hyejin Park
1Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, U.S.A
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Un-ho Jin;
Un-ho Jin
1Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, U.S.A
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Keshav Karki;
Keshav Karki
1Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, U.S.A
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Arul Jayaraman;
Arul Jayaraman
2Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, U.S.A
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Clint Allred;
Clint Allred
3Department of Nutrition, Texas A&M University, College Station, TX 77843, U.S.A
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Sharon K. Michelhaugh;
Sharon K. Michelhaugh
4Fralin Biomedical Research Institute, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, U.S.A
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Sandeep Mittal;
Sandeep Mittal
4Fralin Biomedical Research Institute, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, U.S.A
5Carlion Clinic — Neurosurgery, Roanoke, VA 24014, U.S.A
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Robert S. Chapkin;
Robert S. Chapkin
3Department of Nutrition, Texas A&M University, College Station, TX 77843, U.S.A
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Stephen Safe
1Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, U.S.A
Correspondence: Stephen Safe (ssafe@cvm.tamu.edu)
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Publisher: Portland Press Ltd
Received:
May 28 2020
Revision Received:
August 21 2020
Accepted:
September 08 2020
Accepted Manuscript online:
September 09 2020
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem J (2020) 477 (19): 3899–3910.
Article history
Received:
May 28 2020
Revision Received:
August 21 2020
Accepted:
September 08 2020
Accepted Manuscript online:
September 09 2020
Citation
Hyejin Park, Un-ho Jin, Keshav Karki, Arul Jayaraman, Clint Allred, Sharon K. Michelhaugh, Sandeep Mittal, Robert S. Chapkin, Stephen Safe; Dopamine is an aryl hydrocarbon receptor agonist. Biochem J 16 October 2020; 477 (19): 3899–3910. doi: https://doi.org/10.1042/BCJ20200440
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