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• W2972186560 abstract "The male rat adrenal pheochromocytoma cell-derived PC12 cell line can synthesize and release catecholamine neurotransmitters, and it has been widely used as a model system in cell biology and toxicology research. Catechol-O-methyltransferase (COMT) is involved in the inactivation of the catecholamine neurotransmitters, and it is particularly important for the regulation of dopamine. In this study, we explored the feasibility of using PC12 cells as an in vitro drug screening platform to compare the activity of multiple COMT inhibitors. Incubation of PC12 cells with tolcapone, a highly potent and selective COMT inhibitor, increased the concentrations of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) while reducing the metabolites 3-methoxytyramine (3-MT) and homovanillic acid (HVA) in the cell culture medium. LIBD-3, a novel, non-nitrocatechol COMT inhibitor, produced similar effects compared to tolcapone. LIBD-4, a less potent inhibitor, exhibited the expected right-shift in functional inhibition in the assay. These results match the known in vivo effects of COMT inhibition in rodents. Together, these data support the continued use of PC12 cells as an in vitro screen that bridges cell-free enzyme assays and more costly in vivo assays." @default.
• W2972186560 created "2019-09-12" @default.
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• W2972186560 date "2019-09-06" @default.
• W2972186560 modified "2023-10-12" @default.
• W2972186560 title "Development of a PC12 Cell Based Assay for Screening Catechol-<i>O</i>-methyltransferase Inhibitors" @default.
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• W2972186560 doi "https://doi.org/10.1021/acschemneuro.9b00395" @default.
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