Multidrug resistance-associated protein 1 functions as an efflux pump of xenobiotics in the skin.
OBJECTIVE
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 muM) 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.
Li
Qing
Q
Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa, Japan.
Kato
Yukio
Y
Sai
Yoshimichi
Y
Imai
Teruko
T
Tsuji
Akira
A
D000814:Aniline Compounds; D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D004950:Esterases / Q000378:metabolism; D005456:Fluorescent Dyes; D024841:Fluoroquinolones / Q000493:pharmacokinetics; D015603:Keratinocytes / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D010879:Piperazines / Q000493:pharmacokinetics; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D012867:Skin / Q000201:enzymology / Q000378:metabolism*; D014018:Tissue Distribution; D014966:Xanthenes; D015262:Xenobiotics / Q000378:metabolism*
D000814:Aniline Compounds; D000890:Anti-Infective Agents; D004950:Esterases; D005456:Fluorescent Dyes; D024841:Fluoroquinolones; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010879:Piperazines; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D014966:Xanthenes; D015262:Xenobiotics; C092350:FM 4-64; C059715:Fluo-3; C075375:grepafloxacin; C421109:multidrug resistance-associated protein 1