PMID- 21884716 OWN - NLM STAT- MEDLINE DCOM- 20120113 LR - 20211020 IS - 1096-0333 (Electronic) IS - 0041-008X (Print) IS - 0041-008X (Linking) VI - 257 IP - 1 DP - 2011 Nov 15 TI - Organic anion transporting polypeptides in the hepatic uptake of PBDE congeners in mice. PG - 23-31 LID - 10.1016/j.taap.2011.08.014 [doi] AB - BDE47, BDE99 and BDE153 are the predominant polybrominated diphenyl ether (PBDE) congeners detected in humans and can induce drug metabolizing enzymes in the liver. We have previously demonstrated that several human liver organic anion transporting polypeptides (humans: OATPs; rodents: Oatps) can transport PBDE congeners. Mice are commonly used to study the toxicity of chemicals like the PBDE congeners. However, the mechanism of the hepatic PBDE uptake in mice is not known. Therefore, the purpose of the current study was to test the hypothesis that BDE47, BDE99, and BDE153 are substrates of mouse hepatic Oatps (Oatp1a1, Oatp1a4, Oatp1b2, and Oatp2b1). We used Human Embryonic Kidney 293 (HEK293) cells transiently expressing individual Oatps and quantified the uptake of BDE47, BDE99, and BDE153. Oatp1a4, Oatp1b2, and Oatp2b1 transported all three PBDE congeners, whereas Oatp1a1 did transport none. Kinetic studies demonstrated that Oatp1a4 and Oatp1b2 transported BDE47 with the greatest affinity, followed by BDE99 and BDE153. In contrast, Oatp2b1 transported all three PBDE congeners with similar affinities. The importance of hepatic Oatps for the liver accumulation of BDE47 was confirmed using Oatp1a4-, and Oatp1b2-null mice. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Pacyniak, Erik AU - Pacyniak E AD - Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA. FAU - Hagenbuch, Bruno AU - Hagenbuch B FAU - Klaassen, Curtis D AU - Klaassen CD FAU - Lehman-McKeeman, Lois AU - Lehman-McKeeman L FAU - Guo, Grace L AU - Guo GL LA - eng GR - RR021940/RR/NCRR NIH HHS/United States GR - GM077336/GM/NIGMS NIH HHS/United States GR - P20 RR021940/RR/NCRR NIH HHS/United States GR - R01 GM077336/GM/NIGMS NIH HHS/United States GR - DK081343/DK/NIDDK NIH HHS/United States GR - R01 DK081343-04/DK/NIDDK NIH HHS/United States GR - R01 DK081343/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20110822 PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 0 (2,2',4,4',5-brominated diphenyl ether) RN - 0 (Halogenated Diphenyl Ethers) RN - 0 (Organic Anion Transport Protein 1) RN - 0 (Organic Anion Transporters) RN - 0 (Polybrominated Biphenyls) RN - 0 (hexabrominated diphenyl ether 153) RN - 0N97R5X10X (2,2',4,4'-tetrabromodiphenyl ether) SB - IM MH - Animals MH - Cloning, Molecular MH - Dose-Response Relationship, Drug MH - HEK293 Cells/metabolism MH - Halogenated Diphenyl Ethers/*metabolism MH - Humans MH - Liver/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Organic Anion Transport Protein 1/metabolism MH - Organic Anion Transporters/*metabolism MH - Polybrominated Biphenyls/metabolism PMC - PMC3220748 MID - NIHMS325135 EDAT- 2011/09/03 06:00 MHDA- 2012/01/14 06:00 PMCR- 2012/11/15 CRDT- 2011/09/03 06:00 PHST- 2011/05/17 00:00 [received] PHST- 2011/08/08 00:00 [revised] PHST- 2011/08/13 00:00 [accepted] PHST- 2011/09/03 06:00 [entrez] PHST- 2011/09/03 06:00 [pubmed] PHST- 2012/01/14 06:00 [medline] PHST- 2012/11/15 00:00 [pmc-release] AID - S0041-008X(11)00312-7 [pii] AID - 10.1016/j.taap.2011.08.014 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 2011 Nov 15;257(1):23-31. doi: 10.1016/j.taap.2011.08.014. Epub 2011 Aug 22.