Bile salt exporter pump

Bile salt export pump (BSEP gene symbol ABCB11) mediates the biliary excretion of nonconjugated bile salts, such as taurocholic acid, glycocholic acid and cholic acid, and therefore is responsible for the formation of the bile acid-dependent bile flow [97, 98]. Its hereditary defect results in the acquisition of PFIC2, a potentially lethal disease which requires liver transplantation [17, 81, 82, 99]. As discussed in Section 12.5.2, the inhibition of BSEP following drug administration may result in cholestasis. 

A. F., Meier, P. J., The sister ofP-glycoprotein represents the canalicular bile salt export pump of mammalian liver, J. Biol. Chem. 1998, 273, 10046-10050. 

Funk, C., Ponelle, C., Scheuermann, G., Pantze, M., Cholestatic potential of troglitazone as a possible factor contributing to troglitazone-induced hepatotoxicity in vivo and in vitro interaction at the canalicular bile salt export pump (Bsep) in the rat, Mol. Pharmacol. 2001, 59, 627-635. 

J., Kuliak-Ublick, G. A., Meier, P. J., Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver, Gastroenterology 2000, 118, 422-430. 

H., Sugiyama, Y., Characterization of bile acid transport mediated by multidrug resistance assodated protein 2 and bile salt export pump, Biochim. Biophys. Acta 2001, 1511, 7-16. 

Jansen PL, Strautnieks SS, Jacquemin E, Hadchouel M, Sokal EM, Hooiveld GJ et al. Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. Gastroenterology 1999 117(6) 1370— 1379. 

Mita, S. et al. (2006) Inhibition ofbile add transport across Na + /taurocholate cotransporting polypeptide (SLClOAl) and bile salt export pump (ABCB 11)-coexpressing LLC-PKl cells by cholestasis-inducing drugs. Drug Metabolism and Disposition The Biological Fate of Chemicals, 34 (9), 1575-1581. 

Funk, C. et al. (2001) Troglitazone-induced intrahepatic cholestasis by an interference with the hepatobiliary export ofbile acids in male and female rats. Correlation with the gender difference in troglitazone sulfate formation and ihe inhibition of the canalicular bile salt export pump (Bsep) by troglitazone and troglitazone sulfate. Toxicology, 167 (1), 83-98. 

Meier PJ, Kullak-Ublick G. Sequence analysis of bile salt export pump (ABCB11) and multidrug resistance P-glycoprotein 3 (ABCB4, MDR3) in patients with intrahepatic cholestasis of pregnancy. Pharmacogenetics 2004 14 91-102. 

Wang L, Soroka CJ, Boyer Jl. The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II. J Clin Invest 2002 110 965-972. 

Mita S, Suzuki H, Akita H, et al. Vectorial transport of hile salts across MDCK cells expressing both rat Na+-taurocholate cotransporting polypeptide and rat bile salt export pump. Am J Physiol Gastrointest Liver Physiol 2005 288 G15943167. 

PFIC 2 This gene mutation, which is located on chromosome 2q24, impairs the canalicular bile salt export pump (BSEP), resulting in the accumulation of bile acids in hepatocytes. Laboratory tests show an increase in bile acid, AP and LAP levels with lowered gamma GT and cholesterol levels. Pruritus is common. There is histological evidence of neonatal giant cell hepatitis. Prognosis is poor. 

Fattinger K, Funk C, Pantze M, Weber C, Reichen J, Stieger B, Meier PJ. The endothehn antagonist bosentan inhibits the canahcular bile salt export pump a potential mechanism for hepatic adverse reactions. Clin Pharmacol Ther 2001 69(4) 223-31. 

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