Physiological characteristics of allo-cholic acid

Abstract

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 ␣ -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.

Physicochemical and physiological properties of 5α-cyprinol sulfate, the toxic bile salt of cyprinid fish

“…The addition of a ␤-hydroxy group to chenodeoxycholic acid results in incomplete conjugation with taurine during hepatic transport (40). Efficient transport of tauroallocholate in the anesthetized biliary fistula rat has recently been reported (41) in agreement with our results using the perfused liver.…”

Changes in the expression of genes related to bile acid synthesis and transport by the rat liver during hepatocarcinogenesis

“…The presence of a still active 5α-reductase catalysing the conversion of 3-oxo-4 -steroid intermediates into their respective 3-oxo-5α-structures has been invoked to explain the appearance of allo-BAs in these patients [8]. By contrast, allo-CA is not transported by Bsep, at least for the rat orthologue of this export pump [36]. As happens for flat unsaturated BAs [33], allo-CA transport across the rat canalicular plasma membrane is probably mediated by Mrp2.…”

Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades

“…Such bile acids also occur in mice when the canalicular bile salt export pump (BSEP) has been deleted genetically ( 116 ). been prepared synthetically and some its biological properties explored ( 108 ). Allo bile acids have also been identifi ed in fecal bile acids ( 109 ), presumably generated by bacterial enzymes acting on the 3-oxo-⌬ 4,6 intermediate that is formed during the process of C-7 dehydroxylation ( 110 ).…”