PMID- 22342602
OWN - NLM
STAT- MEDLINE
DCOM- 20120625
LR  - 20211021
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 261
IP  - 1
DP  - 2012 May 15
TI  - Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes.
PG  - 1-9
LID - 10.1016/j.taap.2012.02.002 [doi]
AB  - Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic 
      transport protein-mediated uptake and biliary excretion of substrates. However, 
      little is known about the disposition of endogenous bile acids (BAs) in SCH. In 
      this study, four endogenous conjugated BAs common to rats and humans [taurocholic 
      acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and 
      glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to 
      rodents (alpha- and beta-tauromuricholic acid; alpha/beta TMCA), were profiled in primary rat 
      and human SCH. Using B-CLEAR(R) technology, BAs were measured in cells+bile 
      canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as 
      in vivo, taurine-conjugated BA species were predominant in rat SCH, while 
      glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs 
      remained relatively constant over days in culture in rat SCH. Total BAs in 
      control (CTL) cells+bile, cells, and medium were approximately 3.4, 2.9, and 
      8.3-fold greater in human than in rat. The estimated intracellular concentrations 
      of the measured total BAs were 64.3+/-5.9 muM in CTL rat and 183+/-56 muM in CTL human 
      SCH, while medium concentrations of the total BAs measured were 1.16+/-0.21 muM in 
      CTL rat SCH and 9.61+/-6.36 muM in CTL human SCH. Treatment of cells for 24h with 10 
      muM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the 
      Na(+)-taurocholate cotransporting polypeptide (NTCP), had no significant effect on 
      endogenous BAs measured at the end of the 24-h culture period, potentially due to 
      compensatory mechanisms that maintain BA homeostasis. These data demonstrate that 
      BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to 
      study alterations in BA disposition if species differences are taken into 
      account.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Marion, Tracy L
AU  - Marion TL
AD  - Curriculum in Toxicology, UNC School of Medicine, The University of North 
      Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7270, USA.
FAU - Perry, Cassandra H
AU  - Perry CH
FAU - St Claire, Robert L 3rd
AU  - St Claire RL 3rd
FAU - Brouwer, Kim L R
AU  - Brouwer KL
LA  - eng
GR  - R56 GM041935/GM/NIGMS NIH HHS/United States
GR  - R01 GM041935/GM/NIGMS NIH HHS/United States
GR  - T32-ES007126/ES/NIEHS NIH HHS/United States
GR  - T32 ES007126/ES/NIEHS NIH HHS/United States
GR  - GM41935/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120211
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Chromans)
RN  - 0 (Organic Anion Transporters, Sodium-Dependent)
RN  - 0 (Symporters)
RN  - 0 (Thiazolidinediones)
RN  - 145420-23-1 (sodium-bile acid cotransporter)
RN  - I66ZZ0ZN0E (Troglitazone)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Bile Acids and Salts/*metabolism
MH  - Biological Transport
MH  - Cell Culture Techniques
MH  - Cells, Cultured
MH  - Chromans/pharmacology
MH  - Chromatography, Liquid
MH  - Female
MH  - Hepatocytes/*metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Models, Biological
MH  - Organic Anion Transporters, Sodium-Dependent/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Species Specificity
MH  - Symporters/pharmacology
MH  - Tandem Mass Spectrometry
MH  - Thiazolidinediones/pharmacology
MH  - Troglitazone
MH  - Young Adult
PMC - PMC3679176
MID - NIHMS356659
EDAT- 2012/02/22 06:00
MHDA- 2012/06/26 06:00
PMCR- 2013/06/11
CRDT- 2012/02/21 06:00
PHST- 2011/07/13 00:00 [received]
PHST- 2012/01/10 00:00 [revised]
PHST- 2012/02/02 00:00 [accepted]
PHST- 2012/02/21 06:00 [entrez]
PHST- 2012/02/22 06:00 [pubmed]
PHST- 2012/06/26 06:00 [medline]
PHST- 2013/06/11 00:00 [pmc-release]
AID - S0041-008X(12)00057-9 [pii]
AID - 10.1016/j.taap.2012.02.002 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2012 May 15;261(1):1-9. doi: 10.1016/j.taap.2012.02.002. 
      Epub 2012 Feb 11.