Abstract
The human organic cation transporter 1 (OCT1) is a polyspecific transporter involved in the uptake of positively charged and neutral small molecules in the liver. To date, few endogenous compounds have been identified as OCT1 substrates; more importantly, the effect of drugs on endogenous substrate transport has not been examined. In this study, we established monoamine neurotransmitters as substrates for OCT1, specifically characterizing serotonin transport in human embryonic kidney 293 cells. Kinetic analysis yielded a Km of 197 micomolar and a Vmax of 561 pmol/mg protein/minute for serotonin. Furthermore, we demonstrated that serotonin uptake was inhibited by diphenhydramine, fluoxetine, imatinib, and verapamil, with IC50 values in the low micromolar range. These results were recapitulated in primary human hepatocytes, suggesting that OCT1 plays a significant role in hepatic elimination of serotonin and that xenobiotics may alter the elimination of endogenous compounds as a result of interactions at the transporter level.
Footnotes
- Received September 20, 2013.
- Accepted March 31, 2014.
This work was supported by the National Institutes of Health Institute of General Medical Sciences [Grant R01-GM077335] and [Grant P20 GM103549-07], National Center for Research Resources [Grant P20-RR021940], and National Institute of Environmental Health and Sciences [Grant T32 ES007079-26A2]; and the Kansas IDeA Network of Biomedical Research Excellence [Grant QH846868-K-INBRE].
The study is sponsored by the Kansas University Medical Center, Department of Pharmacology, Toxicology and Therapeutics Biospecimen Core laboratory and the Liver Center at Kansas University Medical Center.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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