Dopamine is an aryl hydrocarbon receptor agonist

• Published in: Biochemical journal Vol. 477; no. 19; p. 3899
• Main Authors: Park, Hyejin, Jin, Un-Ho, Karki, Keshav, Jayaraman, Arul, Allred, Clint, Michelhaugh, Sharon K, Mittal, Sandeep, Chapkin, Robert S, Safe, Stephen
• Format: Journal Article
• Language: English
• Published: England 16.10.2020
• Subjects: Caco-2 Cells; Carbidopa - pharmacology; Cytochrome P-450 CYP1A1 - metabolism; Cytochrome P-450 CYP1B1 - metabolism; Cytochrome P-450 Enzyme Inducers - pharmacology; Dopamine - pharmacology; Glucuronosyltransferase; Humans; Neoplasms - metabolism; Receptors, Aryl Hydrocarbon - agonists; Receptors, Aryl Hydrocarbon - metabolism; selective AhR modulator; pancreatic cancer; glioblastoma; Carbidopa; colon cancer; L-DOPA
• ISSN: 1470-8728
• DOI: 10.1042/BCJ20200440

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.