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Inhibition of the human organic anion transporter 1 by the caffeine metabolite 1-methylxanthine

Caffeine (1,3,7-trimethylxanthine) is daily and widely consumed in beverages and food and is mainly metabolized to 1,7-dimethylxanthine and 1-methylxanthine. Indirect clinical evidence suggests that 1-methylxanthine interacts with the organic anion transport system in the human kidney. In this study...

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Main Authors: Rengelshausen, Jens (Author) , Lindenmaier, Heike (Author) , Cihlar, Tomas (Author) , Walter-Sack, Ingeborg (Author) , Haefeli, Walter E. (Author) , Weiß, Johanna (Author)
Format: Article (Journal)
Language:English
Published: 5 June 2004
In: Biochemical and biophysical research communications
Year: 2004, Volume: 320, Issue: 1, Pages: 90-94
ISSN:1090-2104
DOI:10.1016/j.bbrc.2004.05.142
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.bbrc.2004.05.142
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006291X04011532
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Author Notes:Jens Rengelshausen, Heike Lindenmaier, Tomas Cihlar, Ingeborg Walter-Sack, Walter Emil Haefeli, and Johanna Weiss
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Summary:Caffeine (1,3,7-trimethylxanthine) is daily and widely consumed in beverages and food and is mainly metabolized to 1,7-dimethylxanthine and 1-methylxanthine. Indirect clinical evidence suggests that 1-methylxanthine interacts with the organic anion transport system in the human kidney. In this study the effect of caffeine and its main metabolites on the human organic anion transporter 1 (hOAT1) was investigated using CHO cells overexpressing hOAT1. The uptake of 6-carboxyfluorescein into CHOhOAT cells was significantly inhibited by ⩾100μM of 1-methylxanthine. Five hundred micromolar 1-methylxanthine was equieffective to 100μM probenecid. In contrast, caffeine and 1,7-dimethylxanthine did not inhibit the transport of 6-carboxyfluorescein at concentrations up to 500μM. In conclusion, the caffeine metabolite 1-methylxanthine inhibits the transport activity of hOAT1 in vitro. The central involvement of hOAT1 in the renal excretion of numerous drugs suggests that this inhibition may alter the pharmacokinetics of a series of clinically important drugs in humans.
Item Description:Gesehen am 19.05.2021
Physical Description:Online Resource
ISSN:1090-2104
DOI:10.1016/j.bbrc.2004.05.142

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