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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| Hauptverfasser: | , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
5 June 2004
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| In: |
Biochemical and biophysical research communications
Year: 2004, Jahrgang: 320, Heft: 1, Pages: 90-94 |
| ISSN: | 1090-2104 |
| DOI: | 10.1016/j.bbrc.2004.05.142 |
| Online-Zugang: | 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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| Verfasserangaben: | Jens Rengelshausen, Heike Lindenmaier, Tomas Cihlar, Ingeborg Walter-Sack, Walter Emil Haefeli, and Johanna Weiss |
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| 245 | 1 | 0 | |a Inhibition of the human organic anion transporter 1 by the caffeine metabolite 1-methylxanthine |c Jens Rengelshausen, Heike Lindenmaier, Tomas Cihlar, Ingeborg Walter-Sack, Walter Emil Haefeli, and Johanna Weiss |
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| 520 | |a 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. | ||
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