J. Lipid Res.
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A more recent version of this article appeared on January 1, 2003

Papers In Press, published online ahead of print September 1, 2002
J. Lipid Res., doi:10.1194/jlr.M200220-JLR200
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Submitted on June 5, 2002
Revised on August 19, 2002
Accepted on August 20, 2002

Physiological characteristics of allo-cholic acid

Maria E. Mendoza, Maria J. Monte, Maria A. Serrano, Marçal Pastor-Anglada, Bruno Stieger, Peter J Meier, Manuel Medarde, and Jose J. G. Marin

Physiology and Pharmacology, University of Salamanca, Salamanca, Salamanca 37007

Corresponding Author: jjgmarin{at}usal.es

The physiological characterstics of allo-cholic acid (ACA), a typically fetal bile acid that reappears during liver regeneration and carcinogenesis were investigated. [14C]-Tauro-ACA (TACA) uptake by CHO cells expressing rat Oatp1 or Ntcp was lower than that of [14C]-taurocholic acid (TCA). Although TACA inhibited ATP-dependent TCA transport across plasma membrane vesicles from Sf9 cells expressing rat or mouse Bsep, no ATP-dependent TACA transport was found. In rats, TACA was secreted into bile with no major biotransformation and it had lower clearance and longer half-life than TCA. In mice, TACA bile output was lower (-50%) than that of TCA, whereas TACA induced nine-fold higher bile flow than TCA. Even though the intracellular levels were lower for TACA, translocation into the hepatocyte nucleus was higher for TACA than for TCA. However rate of DNA synthesis, expression levels of a-fetoprotein, albumin, Ntcp and Bsep, cell viability and apoptosis in rat hepatocytes were similarly affected by both isomers. In conclusion, TACA partly shares hepatocellular uptake system(s) for TCA. Furthermore, in contrast to other “flat” bile acids, TACA is efficiently secreted into bile via transport system(s) other than Bsep and is highly choleretic, hence its appearance during certain situations may prevent accumulation of cholestatic precursors.


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