Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, U.S.A.
Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, U.S.A.
Biochem J. 2020 Oct 16;477(19):3899-3910. 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.
色氨酸代谢物表现出芳香烃受体 (AhR) 激动剂活性，最近的研究表明，苯丙氨酸代谢物 5-羟色胺和卡比多巴（一种用于治疗帕金森病的药物）激活了 AhR。在这项研究中，我们确定神经活性激素多巴胺是结肠和神经胶质瘤细胞中细胞色素 P4501A1（CYP1A1）、细胞色素 P4501B1（CYP1B1）和 UGT1A1 等药物代谢酶的诱导剂，卡比多巴也出现了类似的结果。相比之下，卡比多巴而非多巴胺在 BxPC3 胰腺癌细胞中表现出 AhR 活性，而在 Panc1 胰腺癌细胞中，这两种化合物的活性都很小。与之前的一份报告相反，仅在 BxPC3 细胞中高浓度（100μM）时才观察到卡比多巴的诱导反应和细胞毒性。我们的结果表明，与 5-羟色胺和几种色氨酸代谢物类似，多巴胺也是一种 AhR 活性化合物。
