Development of a PC12 Cell Based Assay for Screening Catechol- O-methyltransferase Inhibitors

Gongliang Zhang, Ingrid P. Buchler, Michael Depasquale, Michael Wormald, Gangling Liao, Huijun Wei, James C. Barrow, Gregory V. Carr

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)4221-4226
Number of pages6
JournalACS Chemical Neuroscience
Issue number10
StatePublished - Oct 16 2019


  • PC12 cells
  • catechol-O-methyltransferase
  • dopamine

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology


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