Functional expression of the apical Na+-dependent bile acid transporter in large but not small rat cholangiocytes

Alpini, Gianfranco; Glaser, Shannon; Rodgers, Rebecca; Phinizy, Jo Lynne; Robertson, W.; Lasater, John; Caligiuri, Alessandra; Tretjak, Ziga; LeSage, Gene

doi:10.1053/gast.1997.v113.pm9352879

Cited by 159 publications

(136 citation statements)

References 0 publications

Supporting

Mentioning

130

Contrasting

Unclassified

Order By: Relevance

“…5 We have characterized the transport activity of the apical Na ϩ -dependent bile acid transporter (ASBT) originally described in the ileum in isolated rat cholangio-cytes. 6 In addition, we have shown with immunofluorescence studies that ASBT is present in the apical membrane of large cholangiocytes and large (greater than 15 m in diameter) isolated intrahepatic bile duct units. 6 In isolated bile duct fragments, cholangiocytes absorb bile acids.…”

mentioning

confidence: 82%

“…6 In addition, we have shown with immunofluorescence studies that ASBT is present in the apical membrane of large cholangiocytes and large (greater than 15 m in diameter) isolated intrahepatic bile duct units. 6 In isolated bile duct fragments, cholangiocytes absorb bile acids. 7 Previous studies in bile duct fragments do not address the fate of bile acids after absorption (i.e., entering cholehepatic shunt) and likely have limited predictability for the potential of bile acids absorption in vivo.…”

mentioning

confidence: 82%

“…Taurocholate uptake was determined in isolated cholangiocytes, and estimation of the Michaelis constant (K m ) and maximal velocity (V max ) were determined as we previously described. 6 Na ϩ -independent uptake was calculated by subtracting the background 3 H-TC uptake measured at zero time incubation from uptake in the presence of a Na ϩ -free (equal molar choline substitution ) incubation buffer. Na ϩ -dependent uptake was calculated by subtracting the uptake in the presence of choline from the total uptake in the presence of Na ϩ .…”

Section: Animal Modelmentioning

confidence: 99%

See 2 more Smart Citations

Secretin activation of the apical Na+‐dependent bile acid transporter is associated with cholehepatic shunting in rats†

et al. 2005

View full text Add to dashboard Cite

The role of the cholangiocyte apical Na ؉ -dependent bile acid transporter (ASBT) in bile formation is unknown. Bile acid absorption by bile ducts results in cholehepatic shunting, a pathway that amplifies the canalicular osmotic effects of bile acids. We tested in isolated cholangiocytes if secretin enhances ASBT translocation to the apical membrane from latent preexisting intracellular stores. In vivo, in bile duct-ligated rats, we tested if increased ASBT activity (induced by secretin pretreatment) results in cholehepatic shunting of bile acids. We determined the increment in taurocholate-dependent bile flow and biliary lipid secretion and taurocholate (TC) biliary transit time during high ASBT activity. Secretin stimulated colchicine-sensitive ASBT translocation to the cholangiocyte plasma membrane and 3 H-TC uptake in purified cholangiocytes. Consistent with increased ASBT promoting cholehepatic shunting, with secretin pretreatment, we found TC induced greater-than-expected biliary lipid secretion and bile flow and there was a prolongation of the TC biliary transit time.

show abstract

mentioning

confidence: 82%

mentioning

confidence: 82%

Section: Animal Modelmentioning

confidence: 99%

See 1 more Smart Citation

Secretin activation of the apical Na+‐dependent bile acid transporter is associated with cholehepatic shunting in rats†

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Further analyses of mRNA and protein expression revealed that Asbt is also expressed in the apical membrane of the renal proximal convoluted tubule, where it might be important for tubular reabsorption of bile acids that are filtrated by the glomeruli (Christie et al 1996). Asbt expression was also detected in the apical membrane of cholangiocytes in the liver bile duct epithelium (Alpini et al 1997;Lazaridis et al 1997).…”

Section: Functional Properties and Expression Patterns Of The Individmentioning

confidence: 99%

The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships

Geyer

Wilke

Petzinger

2006

Naunyn Schmied Arch Pharmacol

161

138

View full text Add to dashboard Cite

The solute carrier family 10 (SLC10) comprises two sodium-dependent bile acid transporters, i.e. the Na + / taurocholate cotransporting polypeptide (NTCP; SLC10A1) and the apical sodium-dependent bile acid transporter (ASBT; SLC10A2). These carriers are essentially involved in the maintenance of the enterohepatic circulation of bile acids mediating the first step of active bile acid transport through the membrane barriers in the liver (NTCP) and intestine (ASBT). Recently, four new members of the SLC10 family were described and referred to as P3 (SLC10A3), P4 (SLC10A4), P5 (SLC10A5) and sodium-dependent organic anion transporter (SOAT; SLC10A6). Experimental data supporting carrier function of P3, P4, and P5 is currently not available. However, as demonstrated for SOAT, not all members of the SLC10 family are bile acid transporters. SOAT specifically transports steroid sulfates such as oestrone-3-sulfate and dehydroepiandrosterone sulfate in a sodium-dependent manner, and is considered to play an important role for the cellular delivery of these prohormones in testes, placenta, adrenal gland and probably other peripheral tissues. ASBT and SOAT are the most homologous members of the SLC10 family, with high sequence similarity (∼70%) and almost identical gene structures. Phylogenetic analyses of the SLC10 family revealed that ASBT and SOAT genes emerged from a common ancestor gene. Structure-activity relationships of NTCP, ASBT and SOAT are discussed at the amino acid sequence level.Based on the high structural homology between ASBT and SOAT, pharmacological inhibitors of the ASBT, which are currently being tested in clinical trials for cholesterollowering therapy, should be evaluated for their crossreactivity with SOAT.

show abstract

“…All the intestinal transporters for organic anions are also expressed in human hepatocytes more or less, although ASBT, OATP1A2 and MRP1 appear not to be present in these cells, and little seems to be known about the expression of hepatic MCTs. [50][51][52] However, several additional transporters are expressed in the liver. The majority of these are mainly transporters for organic anions, i.e.…”

Section: Localization In the Enterohepatic Systemmentioning

confidence: 99%

Intestinal transporters for endogenic and pharmaceutical organic anions: the challenges of deriving in-vitro kinetic parameters for the prediction of clinically relevant drug–drug interactions

Grandvuinet

Vestergaard

Rapin³

et al. 2012

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

Objectives This review provides an overview of intestinal human transporters for organic anions and stresses the need for standardization of the various in‐vitro methods presently employed in drug–drug interaction (DDI) investigations. Key findings Current knowledge on the intestinal expression of the apical sodium‐dependent bile acid transporter (ASBT), the breast cancer resistance protein (BCRP), the monocarboxylate transporters (MCT) 1, MCT3‐5, the multidrug resistance associated proteins (MRP) 1–6, the organic anion transporting polypetides (OATP) 2B1, 1A2, 3A1 and 4A1, and the organic solute transporter α/β (OSTα/β) has been covered along with an overview of their substrates and inhibitors. Furthermore, the many challenges in predicting clinically relevant DDIs from in‐vitro studies have been discussed with focus on intestinal transporters and the various methods for deducting in‐vitro parameters for transporters (Km/Ki/IC50, efflux ratio). The applicability of using a cut‐off value (estimated based on the intestinal drug concentration divided by the Ki or IC50) has also been considered. Summary A re‐evaluation of the current approaches for the prediction of DDIs is necessary when considering the involvement of other transporters than P‐glycoprotein. Moreover, the interplay between various processes that a drug is subject to in‐vivo such as translocation by several transporters and dissolution should be considered.

show abstract

Functional expression of the apical Na+-dependent bile acid transporter in large but not small rat cholangiocytes

Cited by 159 publications

References 0 publications

Secretin activation of the apical Na+‐dependent bile acid transporter is associated with cholehepatic shunting in rats†

Secretin activation of the apical Na+‐dependent bile acid transporter is associated with cholehepatic shunting in rats†

The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships

Intestinal transporters for endogenic and pharmaceutical organic anions: the challenges of deriving in-vitro kinetic parameters for the prediction of clinically relevant drug–drug interactions

Contact Info

Product

Resources

About