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ASBT - Apical sodium-dependent bile acid transporter (ASBT)

In cooperation with the University Medicine of Greifswald, Department of Clinical Pharmacology, Primacyt is offering a broad range of stable transfected HEK293 and MDCK2 cells expressing human ASBT.
All cells are validated for expression rates, localization of the overexpressed transporter protein and functionality. We analyze the uptake functions using suitable substrates, inhibiting the uptake by adding the reference inhibitors.

Apical sodium-dependent bile acid transporter (ASBT, also called IBAT, ISBT: gene symbol SLC10A2)) is a Na+- dependent uptake transporter of bile acids and play a important role in the enterohepatic recirculation of bile acids. ASBT is expressed at apical membrane of ileal enterocytes, proximal renal tubule cells and gallbladder epithelial cells. With a reduced protein activity may result in the manifestation of a variety of gastrointestinal disorders.

A cell platform using stable transfected HEK293 cells expressing human ASBT was generated and validated. We analyze the uptake functions using Taurocholate acid, inhibiting the uptake by adding the reference inhibitor chenodeoxylcholate

The apical sodium-dependent bile acid transporter (ASBT, also called IBAT, ISBT: gene symbol SLC10A2)) is a Na+- dependent uptake transporter of bile acids highly expressed in the apical membrane of ileal enterocytes where it plays a crucial role in the enterohepatic recirculation of bile acids and conjugated bile acids. The second highest site of ASBT expression is proximal tubule cells where ASBT-mediated bile acid reabsorption minimizes bile acid loss in the urine. ASBT is also expressed on the apical membrane of cholangiocyte, participating in bile acid return from the lumen of bile ducts to the liver through the periductular capillary plexus (for a review see Claro da Silva et al., 2013).
ASBT consists probably of 7 – 10 transmembrane domains and mediates the transport of unconjugated bile acids and the glycine and taurine conjugates of the primary bile acids. Typically used in vitro substrates are, e.g., taurocholate, cholate, glycochenodeoxycholate, glycodeoxycholate, chenodeoxycholate, glycoursodeoxycholate. No non-bile acid substrates are known so far. However inhibitory effects of calcium channel blockers (nifedipine, isradipine, diltiazem, verapamil), HMG-CoA reductase inhibitors (simvastatin, mevastatin, lovastatin) diuretics (spironolactone, bumetadine, althazide, but not furosemide) and others (dibucaine, indomethacin, mesoridazine, quinine) are discussed (Zheng et al., 2009, Dong et al., 2013 and Grandvuinet et al., 2012).

Literature
Claro da Silva T, Polli JE, Swaan PW: The solute carrier family 10 (SLC10): beyond bile acid transport. Mol Aspects Med., 2013, 34: 252-269. doi: 10.1016/j.mam.2012.07.004.

Zheng X, Ekins S, Raufman JP, Polli JE: Computational models for drug inhibition of the human apical sodium-dependent bile acid transporter. Mol Pharm, 2009, 6: 1591-1603, doi: 10.1021/mp900163d

Dong Z, Ekins S, Polli JE: Structure-activity relationship for FDA approved drugs as inhibitors of the human sodium taurocholate co-transporting polypeptide (NTCP). Mol Pharm, 2013, 10: 1008–1019

Grandvuinet AS, Vestergaard HT, Rapin N, Steffansen B: 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. J Pharm Pharmacol, 2012, 64: 1523–1548