PMID: 9187518Feb 1, 1997Paper

Cholestatic properties and hepatic transport of steroid glucuronides

Drug Metabolism Reviews
Mary VoreL Huang

Abstract

In summary, the data suggest that E217G is transported by both MOAT and P-glycoprotein into bile, but that P-glycoprotein serves as the target site for cholestasis. We postulate that this target site may be accessed from either the intracellular compartment or the canaliculus, and that MOAT serves as the major delivery route for E217G to the canaliculus. At low, physiologic concentrations of E217G, MOAT-mediated excretion into bile is a detoxification mechanism, serving to prevent intracellular accumulation of a toxic metabolite. However, following administration of high, cholestatic doses, MOAT-mediated excretion into bile results in very high concentrations in bile, on the other of 2-3 mM (see Fig. 4). It is likely that the hydrophobic nature of E217G allows it to partition from bile into the canalicular membrane, from which it can access P-glycoprotein and thus induce cholestasis. Much work is still needed to validate this model of E217G cholestasis. Definitive evidence of P-glycoprotein-mediated transport of E217G must be obtained in cell lines transfected with P-glycoprotein where MRP is absent. More importantly, the mechanism by which interaction of E217G with P-glycoprotein influences bile flow is unknown. Higgins and co...Continue Reading

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Citations

Feb 16, 2002·In Vitro & Molecular Toxicology·M K McMillianM D Johnson
Oct 31, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·L HuangM Vore
Jun 28, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·L HuangM Vore
Apr 7, 2006·Molecular Nutrition & Food Research·Erika PfeifferManfred Metzler
Sep 4, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Andrea C BoaglioMarcelo G Roma
Oct 12, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Andrés E ZucchettiEnrique J Sánchez Pozzi
Mar 10, 2001·Clinics in Liver Disease·G A Kullak-Ublick, P J Meier
Jan 4, 2005·The Veterinary Clinics of North America. Small Animal Practice·Sharon A Center
Aug 21, 2015·Evidence-based Complementary and Alternative Medicine : ECAM·Xiaowei XueJingdong Xu
Jul 30, 2005·Carcinogenesis·Erika PfeifferManfred Metzler
Apr 20, 2006·Pflügers Archiv : European journal of physiology·Ronald P J Oude Elferink, Coen C Paulusma
May 17, 2019·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Glyn Steventon
Mar 21, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Agostina AriasAldo D Mottino
Mar 29, 2003·The Journal of Pharmacology and Experimental Therapeutics·Enrique J Sánchez PozziAldo D Mottino
Sep 25, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Agnes KarasikFlóra Szeri
Nov 16, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Gladys R Rios, Thomas R Tephly
Apr 22, 2003·The Journal of Biological Chemistry·Adrienn BodoBalazs Sarkadi
Feb 2, 2013·Digestive Diseases and Sciences·Andrés E ZucchettiEnrique J Sánchez Pozzi
Mar 23, 2000·Journal of Hepatology·G A Kullak-UblickG Paumgartner
Dec 31, 2003·Gastroenterology·Gerd A Kullak-UblickPeter J Meier
Mar 15, 2006·Gastroenterology·Ronald P J Oude ElferinkAlbert K Groen
Nov 9, 2006·Journal of Agricultural and Food Chemistry·Erika PfeifferManfred Metzler

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