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.
Dopamine is an aryl hydrocarbon receptor agonist
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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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