Multidrug resistance associated protein 1 (MRP1) 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. © 2005 Springer Science + Business Media, Inc.