Physiological characteristics of allo-cholic acid.
The physiological characterstics of allo-cholic acid (ACA), a typically fetal bile acid that reappears during liver regeneration and carcinogenesis were investigated. [(14)C] 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 [(14)C]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 alpha-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.
Mendoza
Maria E
ME
Department of Physiology and Pharmacology, University of Salamanca, Spain.
Monte
Maria J
MJ
Serrano
Maria A
MA
Pastor-Anglada
Marçal
M
Stieger
Bruno
B
Meier
Peter J
PJ
Medarde
Manuel
M
Marin
Jose J G
JJ
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001711:Biotransformation; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent; D051381:Rats; D027981:Symporters; D013656:Taurocholic Acid / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; C490549:Abcb11 protein, mouse; C490548:Abcb11 protein, rat; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter; D013656:Taurocholic Acid