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Multidrug Resistance—Associated Protein 1 Functions as an Efflux Pump of Xenobiotics in the Skin

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Purpose

Recent research has identified gene expression of several types of xenobiotic transporters in the skin. The aim of this study was to investigate whether multidrug resistance–associated protein 1 (MRP1) functions in the skin.

Methods

The distribution of [14C]grepafloxacin in vivo and the transport of 1-[2-amino-5-(2,7-dichloro-6-hydroxy-3-oxo-9-xanthenyl)phenoxy]-2-(2-amino-5-methylphenoxy)ethane-N,N,N′,N′-tetraacetic acid (fluo 3) were examined in the skin of Mrp1 knockout mice [FVB/Mrp1(−/−)] and normal mice [FVB/Mrp1(+/+)].

Results

The tissue-to-plasma concentration ratio of [14C]grepafloxacin was higher in the skin of FVB/Mrp1(−/−) mice than that of FVB/Mrp1(+/+) mice. In skin slices of hairless mouse incubated with fluo 3 pentaacetoxymethyl ester, the accumulation of fluo 3 was significantly increased in the presence of probenecid (2 mM) and carbonyl cyanide p-trifluoromethoxyphenylhydrazone (5 μM) in a time-dependent manner but did not change in the presence of tetraethylammonium (2 mM). In FVB/Mrp1(−/−) mouse skin, the accumulation of fluo 3 increased time-dependently, while no increase was observed in FVB/Mrp1(+/+) mouse skin.

Conclusions

These findings suggest that Mrp1 is involved in the efflux of [14C]grepafloxacin and fluo 3 in the skin, possibly acting as part of a barrier system against xenobiotic compounds.

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Authors and Affiliations

  1. Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa, Japan

    Qing Li, Yukio Kato, Yoshimichi Sai & Akira Tsuji

  2. Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan

    Teruko Imai

Authors
  1. Qing Li
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  2. Yukio Kato
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  3. Yoshimichi Sai
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  4. Teruko Imai
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  5. Akira Tsuji
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Correspondence to Akira Tsuji.

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Li, Q., Kato, Y., Sai, Y. et al. Multidrug Resistance—Associated Protein 1 Functions as an Efflux Pump of Xenobiotics in the Skin. Pharm Res 22, 842–846 (2005). https://doi.org/10.1007/s11095-005-4576-1

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  • DOI: https://doi.org/10.1007/s11095-005-4576-1

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