title: Multidrug resistance-associated protein 1 functions as an efflux pump of xenobiotics in the skin.
abstract: 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.
authors.affiliation: Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa, Japan.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Sai
authors.forename: Teruko
authors.initials: T
authors.lastname: Imai
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuji
mesh_terms: 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*
chemical_list: 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