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NTCP (SLC10A1)

Molecular structure and Tissue distribution
As the first member of the SLC10 family, the Na+/taurocholate co-transporting polypeptide was isolated from rat liver mRNA by expression cloning using the Xenopus laevis oocytes expression system. Further orthologs were subsequently cloned from human, mouse and rabbit livers. The human NTCP gene is located on chromosome 14q24.
NTCP is exclusively expressed at the basolateral (sinusoidal) membrane of hepatocytes. Here, it mediates sodium-coupled uptake of taurocholate and other bile acids with a Na+:taurocholate stoichiometry of 2:1. More recently, expression of rat Ntcp was also detected in the luminal membrane of pancreatic acinar cells.  NTCP/Ntcp expression is regulated by a complex interplay of several ligand-activated receptors (retinoic acid receptor RARα, glucocorticoid receptor) and hepatic transcription factors (hepatocyte nuclear factors HNF1α, HNF4α, and HNF3β and small heterodimer partner SHP-1). This regulation is of particular interest under cholestatic conditions, where down-regulation of Ntcp contributes to the reduced hepatocellular accumulation of potentially toxic bile acids.

Interaction of NTCP with endogenous compounds and drugs
The transport functions of NTCP were extensively studied inNTCP several cell systems. In general, this carrier transports all physiological dihydroxy and trihydroxy bile acids, with a preference for the taurine and glycine conjugates above the unconjugated forms. Furthermore, affinities and uptake rates for the dihydroxy bile acids (e.g. taurochenodeoxycholate, taurodeoxycholate) were normally higher than for the trihydroxy bile acids (i.e. cholate, taurocholate and glycocholate). Due to the transport characteristics and expression pattern, NTCP is essentially involved in the maintenance of the enterohepatic circulation of bile acids mediating the first step in the cellular uptake of bile acids through the membrane barriers in the liver. NTCP is not limited strictly to bile aids. NTCP also transports steroid sulfates like oestrone-3-sulfate, DHEAS, Chenodeoxycholate-3-sulfate and drug such as chlorambucil-taurocholate, Cycloporin (R)- (S)-proprandol and the diuretics furosemide. However, in comparison to the transport of bile acids, NTCP-mediated uptake of steroid sulfates is relatively low.

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New validated products:

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3rd German Pharm-Tox Summit
Göttingen, Germany
26 February - 1 March 2018


Pharmaforum
Saarbrücken, Germany
8 March 2018

 

AAPS Workshop
Virginia, USA
16 - 18 April 2018

 

20th Barrier- and
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Bad Herrenalb, Germany
7 - 9 May 2018

Greifswalder Transporttage 2018
Greifswald, Germany
October 2018

 


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