title: Transport activity of human MRP3 expressed in Sf9 cells: comparative studies with rat MRP3.
abstract: OBJECTIVE
  Multidrug resistance-associated protein 3 (MRP3) was initially cloned as a hepatic transporter induced under cholestatic/ hyperbilirubinemic conditions. In the present study, transport property of human MRP3 (hMRP3) was compared with that of rat MRP3 (rMRP3).
  
  
  METHODS
  Adenosine 5' triphosphate (ATP)-dependent uptake of several organic anions into the membrane vesicles isolated from the Sf9 cells expressing hMRP3 and rMRP3 was measured by rapid filtration technique.
  
  
  RESULTS
  ATP-dependent uptake of glucuronide conjugates, glutathione conjugates. and [3H]methotrexate (MTX) was stimulated by infection of cDNAs for hMRP3 and rMRP3. The mean (+/- SE) Km values for the uptake of 17beta estradiol 17beta-D-glucuronide ([3H]E(2)17 betaG) by hMRP3 and rMRP3 were 42.9 +/- 4.3 microM and 33.4 +/- 2.2 microM, respectively. Although the Ki values of glucuronides on the uptake of E217betaG were similar in humans and rats, hMRP3 exhibited higher Ki values toward MTX. In addition, although glycocholate and taurolithocholate 3-sulfate (TLC-S) were transported by both hMRP3 and rMRP3, taurocholate was only transported to a significant degree by rMRP3. Moreover, the inhibitory effect of taurocholate and glycocholate on the transport of E(2)17beta3G was much more potent in rMRP3 compared to hMRP3.
  
  
  CONCLUSIONS
  Collectively, the substrate specificity of hMRP3 resembles that of rMRP3 although differences were observed, particularly in bile acid transport.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Akita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hirohashi
authors.forename: Hajime
authors.initials: H
authors.lastname: Takikawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sugiyama
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000502:physiology*; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005822:Genetic Vectors; D020719:Glucuronides / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008727:Methotrexate / Q000378:metabolism; D051381:Rats; D013379:Substrate Specificity
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D020719:Glucuronides; D000255:Adenosine Triphosphate; C095122:multidrug resistance protein 3; D005978:Glutathione; D008727:Methotrexate