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Journal of Lipid Research, Vol. 44, 84-92, January 2003
Copyright © 2003 by Lipid Research, Inc.

Physiological characteristics of allo-cholic acid¹

Maria E. Mendoza^*, Maria J. Monte^*, Maria A. Serrano, Marçal Pastor-Anglada, Bruno Stieger^**, Peter J. Meier^**, Manuel Medarde and Jose J. G. Marin^2,*

^* Department of Physiology and Pharmacology, University of Salamanca, Spain
Department of Biochemistry and Molecular Biology, University of Salamanca, Spain
Department of Biochemistry and Molecular Biology, University of Barcelona, Spain
^** Department of Clinical Pharmacology, University of Zurich, Switzerland
Department of Pharmaceutical Chemistry, University of Salamanca, Spain

² To whom correspondence should be addressed. e-mail: 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 Chinese hamster ovary cells expressing rat organic anion transporter polypeptide (Oatp)1 or sodium-taurocholate cotransporter polypeptide (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 bile salt export pump (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 9-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 -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.

Abbreviations: ACA, allo-cholic acid; FP, alpha-fetoprotein; Bsep, bile salt export pump; CA, cholic acid; GCDCA, glycochenodeoxycholic acid; GC-MS, gas-chromatography mass-spectrometry tandem; Ntcp, sodium-taurocholate cotransporter polypeptide; Oatp, organic anion transporter polypeptide; TACA, tauro-allo-cholic acid; TCA, taurocholic acid; UDCA, ursodeoxycholic acid

Supplementary key words bile • liver • steroid

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