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; Jose J.G. Marin

Journal of Lipid Research (Jan 2003)

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,
Jose J.G. Marin

Affiliations

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

Journal volume & issue: Vol. 44, no. 1
pp. 84 – 92

Abstract

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The physiological characterstics of allo-cholic acid (A91), 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 α-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.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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