Apical sodium-dependent bile

Buhman, K. K., Furumoto, E. J., Donkin, S. S., and Story, J. A. (2000). Dietary psyllium increased expression of ileal apical sodium-dependent bile acid transporter mRNA coordinately with dose-responsive changes in bile acid metabolism in rats. J. Nutr. 130, 2137-2142. 

Figure 2.3 Absorption of bile acids by the cholangiocyte in the cholehepatic shunt. Bile acids are absorbed at the apical membrane of the cholangioc5de by the apical sodium-dependent bile-acid transporter (ASBT) that causes cholehepatic shunting of bile acids back to the hepatocyte. Absorbed bile adds are exported across the basolateral membrane by multi-drug-resistance-associated protein 3 (MRP3), a truncated form of ASBT or by the het-eromeric organic solute (OST) a and p forms. Bile adds cause choleresis that is rich in bicarbonate ions secreted by the chloride/bicarbonate ion exchanger.

Apical Sodium-Dependent Bile-Acid Transporter (ASBT)... 

ASBT apical sodium-dependent bile-acid transporter... 

A series of novel benzothiepines (3R,3R -2,3,4,5-tetrahydro-5-aryl-l-benzothiepin-4-ol 1,1-dioxides) were synthesized by cyclization of arylsulfone aldehydes with KOBu. They are tested for their ability as apical sodium dependent bile acid transporter inhibitors <2005JMC5837, 2005JMC5853>. This class of benzothiepine is one of the most potent classes of inhibitors discovered to date. 

Exceptions from Lipinski s rule, i.e., molecules of PSA values > 140 A2 are found to be actively absorbed by carrier-mediated transport systems (Wessel et al. 1998), as shown in Fig. 3. IB. As further detailed in Fig. 3.2, the intestinal epithelium expresses a number of such transport systems for amino acids, organic anions and cations, nucleosides, and hexoses. Among these systems are the apical sodium-dependent bile acid transporter (ASBT Annaba et al. 2007), the monocarboxylate transporter (MCT Halestrap and Price 1999), the sodium-D-glucose co-transporter (SFGT1 Kipp et al. 2003), and the nucleotide transporter SPNT1 (Balimane and Sinko 1999). In addition, the expression of a specialized transporter system for small peptides has been found in the intestinal epithelium with the di/tripeptide transporter, PepTl (Tsuji 2002), after previous functional studies by Hu et al. (1989), and the cloning of PepTl... 

Balakrishnan, A. and Polli, J.E. (2006) Apical sodium dependent bile acid transporter (ASBT, SLC10A2) a potential prodrug target Molecular Pharmacology,... 

Apical sodium-dependent bile acid ASBT (SLC10A2) [77, 78]... 

Chen, F., Ma, L., Dawson, P. A., Sinai, C. J., Sehayek, E., Gonzalez, F. J., Breslow, J., Ananthanarayanan, M., and Shneider, B. L. (2003) Liver receptor homologue-1 mediates species- and cell line-specific bile acid-dependent negative feedback regulation of the apical sodium-dependent bile acid transporter../. Biol. Chem. 278, 19909-19916. 

Jung, D., Fried, M., and Kullak-Ublick, G. A. (2002) Human apical sodium-dependent bile salt transporter gene (SLC10 A2) is regulated by the peroxisome proliferator-activated receptor alpha. J. Biol. Chem. 277, 30559-30566. 

ABC, ATP-binding cassette transporter superfamily ASBT, apical sodium-dependent bile salt transporter BCRP, breast cancer resistance protein BSEP, bile salt export pump MDRl, multidrug resistance MRR multidrug resistance-related protein NTCP, sodium taurocholate cotransporting polypeptide OAT, organic anion transporter OCT, organic cation transporter SLC, solute-linked carrier transporter family SLCO, solute-linked carrier organic anion transporter family. 

TL5956). Dihydrobenzothiazepine 205, derived from a two-step cyclocondensation process, underwent an iridium-catalyzed asymmetric hydrogenation reaction to afford, after chromatography, the desired diastereomer 206 (a late-stage intermediate in the synthesis of a benzothiazepinylphos-phonic acid found to be a nonabsorbable apical sodium-dependent bile acid transporter) (13JOC12726). 

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