Genetic variations of bile salt transporters

2014 ◽  
Vol 12 ◽  
pp. e55-e67 ◽  
Author(s):  
Ralf Kubitz ◽  
Carola Dröge ◽  
Stefanie Kluge ◽  
Jan Stindt ◽  
Dieter Häussinger
Keyword(s):  
Bile Salt ◽  
Genetic Variations ◽  
Bile Salt Transporters

Effect of adjuvant-induced systemic inflammation in rats on hepatic disposition kinetics of taurocholate

2011 ◽  
Vol 300 (1) ◽  
pp. G130-G136 ◽  
Author(s):  
Michael S. Roberts ◽  
Xin Liu ◽  
Yuhong Zou ◽  
Gerhard A. Siebert ◽  
Ping Chang ◽  
...  
Keyword(s):  
Bile Salt ◽  
Mrna Expression ◽  
Rate Constant ◽  
Systemic Inflammation ◽  
Atp Content ◽  
Influx Rate ◽  
Hepatic Disposition ◽  
Disposition Kinetics ◽  
Bile Salt Transporters ◽  
Kinetics Of

It has been reported that the adjuvant-induced inflammation could affect drug metabolism in liver. Here we further investigated the effect of inflammation on drug transport in liver using taurocholate as a model drug. The hepatic disposition kinetics of [3H]taurocholate in perfused normal and adjuvant-treated rat livers were investigated by the multiple indicator dilution technique and data were analyzed by a previously reported hepatobiliary taurocholate transport model. Real-time RT-PCR was also performed to determine the mRNA expression of liver bile salt transporters in normal and diseased livers. The uptake and biliary excretion of taurocholate were impaired in the adjuvant-treated rats as shown by decreased influx rate constant kin (0.65 ± 0.09 vs. 2.12 ± 0.30) and elimination rate constant kbe (0.09 ± 0.02 vs. 0.17 ± 0.04) compared with control rat group, whereas the efflux rate constant kout was greatly increased (0.07 ± 0.02 vs. 0.02 ± 0.01). The changes of mRNA expression of liver bile salt transporters were found in adjuvant-treated rats. Hepatic taurocholate extraction ratio in adjuvant-treated rats (0.86 ± 0.05, n = 6) was significantly reduced compared with 0.93 ± 0.05 ( n = 6) in normal rats. Hepatic extraction was well correlated with altered hepatic ATP content ( r2 = 0.90). In conclusion, systemic inflammation greatly affects hepatic ATP content/production and associated transporter activities and causes an impairment of transporter-mediated solute trafficking and pharmacokinetics.

Genetic Variations of the ABC Transporter Gene ABCB11 Encoding the Human Bile Salt Export Pump (BSEP) in a Japanese Population

2009 ◽  
Vol 24 (3) ◽  
pp. 277-281 ◽  
Author(s):  
Su-Ryang Kim ◽  
Yoshiro Saito ◽  
Masaya Itoda ◽  
Keiko Maekawa ◽  
Manabu Kawamoto ◽  
...  
Keyword(s):  
Bile Salt ◽  
Abc Transporter ◽  
Japanese Population ◽  
Genetic Variations ◽  
Transporter Gene ◽  
Bile Salt Export Pump ◽  
Human Bile

Bile Salt Transporters: Molecular Characterization, Function, and Regulation

2003 ◽  
Vol 83 (2) ◽  
pp. 633-671 ◽  
Author(s):  
Michael Trauner ◽  
James L. Boyer
Keyword(s):  
Bile Salt ◽  
Molecular Characterization ◽  
Bile Salts ◽  
Organic Anion ◽  
Transport Proteins ◽  
Salt Transport ◽  
Transport Systems ◽  
Cholestatic Liver Disease ◽  
Bile Salt Transporters ◽  
Bile Salt Transport

Molecular medicine has led to rapid advances in the characterization of hepatobiliary transport systems that determine the uptake and excretion of bile salts and other biliary constituents in the liver and extrahepatic tissues. The bile salt pool undergoes an enterohepatic circulation that is regulated by distinct bile salt transport proteins, including the canalicular bile salt export pump BSEP (ABCB11), the ileal Na+-dependent bile salt transporter ISBT (SLC10A2), and the hepatic sinusoidal Na+- taurocholate cotransporting polypeptide NTCP (SLC10A1). Other bile salt transporters include the organic anion transporting polypeptides OATPs (SLC21A) and the multidrug resistance-associated proteins 2 and 3 MRP2,3 (ABCC2,3). Bile salt transporters are also present in cholangiocytes, the renal proximal tubule, and the placenta. Expression of these transport proteins is regulated by both transcriptional and posttranscriptional events, with the former involving nuclear hormone receptors where bile salts function as specific ligands. During bile secretory failure (cholestasis), bile salt transport proteins undergo adaptive responses that serve to protect the liver from bile salt retention and which facilitate extrahepatic routes of bile salt excretion. This review is a comprehensive summary of current knowledge of the molecular characterization, function, and regulation of bile salt transporters in normal physiology and in cholestatic liver disease and liver regeneration.

992 IMPACT OF INTRAVENOUS GLUCOSE LOAD ON BILE SALT TRANSPORTERS IN CRITICALLY ILL RABBITS

2010 ◽  
Vol 52 ◽  
pp. S383
Author(s):  
Y.-M. Vanwijngaerden ◽  
S. Derde ◽  
A. Keereman ◽  
L. Langouche ◽  
L. Mebis ◽  
...  
Keyword(s):  
Bile Salt ◽  
Critically Ill ◽  
Glucose Load ◽  
Intravenous Glucose ◽  
Bile Salt Transporters ◽  
Intravenous Glucose Load

Effects of bile salt flux variations on the expression of hepatic bile salt transporters in vivo in mice

2002 ◽  
Vol 37 (5) ◽  
pp. 556-563 ◽  
Author(s):  
Henk Wolters ◽  
Baukje M Elzinga ◽  
Julius F.W Baller ◽  
Renze Boverhof ◽  
Margrit Schwarz ◽  
...  
Keyword(s):  
Bile Salt ◽  
Salt Flux ◽  
Hepatic Bile ◽  
Bile Salt Transporters

Bile Salt Transporters

2002 ◽  
Vol 64 (1) ◽  
pp. 635-661 ◽  
Author(s):  
Peter J. Meier ◽  
B. Stieger
Keyword(s):  
Bile Salt ◽  
Bile Salt Transporters
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