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NTCP - Sodium Taurocholate Cotransporting Polypeptide


Start your Project and why you should contact us.

Primacyt is a functional precision service organization in the field of NTCP. We offer a broad portfolio of transporter assays for NTCP. We support industry, research organizations and government in the field of in vitro studies related to drug interaction from the beginning of your projects until preclinical completion.

Primacyt is your partner for transferring knowledge and expertise for further evolution of absorption, distribution, metabolism, and excretion of potential drug candidates. We are highly committed to offering additional categories of laboratory services and analytical topics as a commitment to the continuous expansion of our leading position in the industry.

We are your partner and the partner of your clients in the education, training, and development of testing protocols. We also offer permanent routine lab services as a customized approach and service. You are in a position to open up additional revenue streams for your organization and partners. Our partners contact us for getting advice on many questions and facts related to

• NTCP, enterohepatic recirculation, NTCP inhibitors, NTCP assays, NTCP transporters,
• Sodium taurocholate, bsep, sodium-dependent amino acid transporters and more.

Primacyt is an expert company in cell technologies with number one focus on hepatocytes. It is logical for our worldwide customers to combine our product preferences with our adequate service products. We are your partner when it comes to questions about drug-drug interaction or related lab service work for drug development.



NTCPs in 30 seconds.

Primacyt is a functional precision service organization in the field of NTCP. We offer a broad portfolio of transporter assays for NTCP. We support industry, research organizations and government in the field of in vitro studies related to drug interaction from the beginning of your projects until preclinical completion.

Sodium (Na+) taurocholate cotransporting polypeptide (NTCP, gene symbol SLC10A1) belongs to the solute carrier family of transporters (SLC10A1) and is expressed on the blood side of the basolateral membrane of hepatocytes. NTCP is also known as liver bile acid transporter LBAT.

Research and development related to NTCPs are lower than for other transporter families. The critical areas of interest are related to hepatitis B, normal tissue complications and bile acids.

Hepatitis B


NTCPs are known to be found on hepatocytes from human, rat, Chinese hamster, and cynomolgus monkey. NTCP is so far not detected in any other tissue; however, transfected cell line expressing the mouse NTCP are desirable.

Bile Acids

The Na+-Taurocholate Cotransporting Polypeptide (NTCP) transporter is involved in the disposition and recirculation of bile acids. It transports in a sodium-dependent manner predominantly bile acids from the sinusoidal membrane. It serves to bring bile salts and other substrates from the bloodstream into the liver. Bile salts are secreted into the bile. They are subject to the re-absorption process entering the portal circulation. NTCPs are moving them back into the liver finally.


Apart from the transport of bile acids (e.g., taurocholate, cholate, glycoursodeoxycholate, and tauroursodeoxycholate), NTCP is also a transporter of bromosulfophthalein (BSP), estrone-3-sulfate or statins and thyroid hormones.

Enterohepatic Circulation

NTCP is one of the key transporters in the enterohepatic circulation of bile acids. As it is an essential hepatic bile acids transporter, inhibition by drugs may be relevant to hepatotoxicity.

Transport is sodium dependent and electrogenic. Regulation of NTCP copes with changes in bile salt load and expression levels decreases when challenged by a high concentration of bile salts. NTCO is not a prominent drug transporter, but is a transporter of the widely prescribed, hepatically acting, HMG-CoA reductase inhibitors, notably statins, hence increasing the risk of drug-drug interactions (DDI).

Project Schedule - How we can work together
Primacyt Cell Culture GmbH provides cell culture solutions for biomedical and cell biology research. PRIMACYT is focused on in-vitro-technologies, certified according to GLP. Our focus is in the fields of hepatocytes, subcellular fractions, skin tissues, cell culture media, 2D and 3D cultures, collagen products, and SILAC media solutions. We provide solutions for human and animal research.

According to the needs of your organization, we can agree on a mutual confidentiality agreement. We discuss your project needs and send you the first offer with the contractually relevant project details.

Our past cooperation partners foresee different needs for the formal contracts the parties need to agree upon. As typically our joint projects are relatively uncomplicated relative to drug discovery projects, we suggest a simple, fast-track approach to save your time for the benefit of your projects.

We are in a position to provide umbrella type contract versions, followed by a project amendment or package everything in a single document. We are prepared to send you templates for such agreements including material transfer agreements when needed. Contract languages can be English or German for you as a commercial or government / academic entity.

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Applications of NTCP Assays
Human hepatitis B virus (HBV) and its satellite for hepatitis D (HDV), are important human pathogens. Available therapeutics against HBV are limited, and no drug is clinically available for HDV infection. A liver bile acids transporter (sodium taurocholate cotransporting polypeptide [NTCP]) is critical for maintaining homeostasis of bile acids and serves as a functional receptor for HBV and HDV.

The binding of the myr-preS1 peptide to NTCP is an initiating step of HBV infection. It has been investigated if this process interferes with the physiological bile acid transport function of NTCP.


Myr-preS1 virus binding to NTCP, necessary for productive HBV infection, interferes with the physiological bile acid transport function of NTCP. Therefore, HBV infection via NTCP may be lockable by NTCP substrates and NTCP-inhibiting drugs. This opens a completely new way for efficient management of HBV infection by the use of NTCP-directed drugs.

Regulation of Bile Salts in Liver

The Presence of NTCP in membrane rafts obtained from mouse liver was studied by immunoblotting and immunofluorescence. HEK-293 cells stably transfected with rat NTCP were used for in vitro studies.

As a result, NTCP localized primarily to membrane rafts in in vivo studies and localized partially in membrane rafts in transfected HEK-293 cells. In these cells, membrane cholesterol depletion resulted in a shift of NTCP localization into non-membrane rafts, which correlated with a 2.5-fold increase in taurocholate transport. Cholesterol repletion shifted back part of NTCP into membrane rafts and normalized taurocholate transport to values similar to control cells.

NTCP localizes in membrane rafts, and its localization and function are regulated by membrane cholesterol content. This may serve as a novel regulatory mechanism of bile salt transport in the liver.

Selected List of substrates and inhibitors
Substrate
Inhibitor
Taurochloric acid
  • Pioglitazone
  • Cyclosporin A
  • Bromosulfothalin
Chlyl-Lysil-Fluorescin

Cholate

Taurocholate, DHEAS
CSA,
Propranolol,
Furosemide,
Ketoconazole,
Rifamycin,
Glibenclamide,
Ritonavir,
Bosentan,
Efavirenz,
Saquinavir

Clinical Significance
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NTCPs plays an essential role for mediating the hepatic uptake of hepatically acting reductase inhibitors. Inhibition of NTCP is, therefore, a significant factor in the development of clinically relevant DDIs.

NTCP expression is typically downregulated in human liver disease. In liver samples derived from patients with progressive familial intrahepatic cholestasis (PFIC), NTCP was downregulated at the level of the proteins, however, not to the mRNA level, indicating a post-translational regulation of NTCP.
A reduction in functional NTCP activity resulting from inhibition or decreased expression levels due to physiological or pathophysiological conditions may lead to reduced bile acid uptake and causes cholestasis or hyperbilirubinemia, or aggravate the condition.


Selected Top 10 Articles for NTCP Aassays
Literature
Selected Top 10 NTCP Science Papers about NTCPs since 2015

Since 2015, the top 3 fields for NTCPs are in the areas of hepatitis B virus (29%), Normal tissue complications (25%) and bile acid (14%). Source: WorldWideScience.ORG.

Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a functional receptor for hepatitis B virus (HBV). Expressing human NTCP in human hepatoma HepG2 cells (HepG2-NTCP) renders these cells susceptible for HBV infection.

Recent studies have revealed that human sodium taurocholate cotransporting polypeptide (SLC10A1 or NTCP) is a functional cellular receptor for hepatitis B virus (HBV). However, whether human NTCP can support HBV infection in mouse hepatocyte cell lines has not been clarified.

NTCP is specifically expressed on the basolateral membrane of hepatocytes, participating in the enterohepatic circulation of bile salts, especially conjugated bile salts, to maintain bile salts homeostasis.

The sodium taurocholate co-transporting polypeptide (NTCP, SLC10A1) is the main hepatic transporter of conjugated bile acids, and the entry receptor for hepatitis B virus (HBV) and hepatitis delta virus (HDV). Myrcludex B, a synthetic peptide mimicking the NTCP-binding domain of HBV, effectively blocks HBV and HDV infection.

Chronic hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are the leading causes of liver disease and cancer worldwide. Recently, the solute carrier and sodium taurocholate co-transporter NTCP has been identified as a receptor for HBV and HDV. Here, we uncover NTCP as a host factor regulating HCV infection.

Sodium taurocholate-cotransporting polypeptide (NTCP) is considered to be a major determinant of bile acid uptake into hepatocytes. However, the regulation of NTCP and the degree that it participates in the accumulation of specific substrates are not well understood.

The sodium-taurocholate cotransporting polypeptide (NTCP) is both a key bile acid (BA) transporter mediating uptake of BA into hepatocytes and an essential receptor for hepatitis B virus (HBV) and hepatitis D virus (HDV).

Sodium taurocholate cotransporting polypeptide (NTCP), encoded by gene SLC10A1, is a receptor for hepatitis B virus (HBV). The aim of the current study was to investigate the role of NTCP polymorphisms in HBV susceptibility, cirrhosis and hepatocarcinogenesis.

Novel sodium taurocholate cotransporting polypeptide (NTCP) inhibitor

Sodium-taurocholate cotransporting polypeptide (NTCP) and bile salt export pump (Bsep) are two key transporters for hepatic bile acid uptake and excretion. Alterations in NTCP and Bsep expression have been reported in pathophysiological conditions.

Overview of Primacyt NTCP Assay
Our assay service for NTCP transporter assay is based on the human transporter for drugs or drug candidates. We offer two assay versions :
  • Determination of the uptake of a test compound
  • Assessment of the inhibitory potential of the test compound compared to a reference substrate.


Our cell platform uses stable transfected HEK293 cells expressing NTCP, demonstrated below.

The uptake function of NTCP is analyzed with CLF (Cholyl-Lysyl-Fluorescein). CLF is mainly secreted into bile canaliculi by the Bile Salt Efflux Pump BSEP.

The uptake function of NTCP is analyzed with Cholyl-Lysyl-Fluorescein (CLF) as a reference substrate. The substrate affinity of the transporter for CLF was determined with a Km value of about 1.7 µmol/L and a maximal capacity of approximately 2.9 pmol CLF /mg protein x sec. The addition of the reference inhibitor Cholate inhibited the uptake of CLF with halfmaximal effects (IC50 value) at a concentration of about 7.3 µmol/L.

We can not make statements about specific diseases. Here we present only a model system for determining the transport of test substances by a particular transporter. We use CLF and Cholate as a model substrate, respectively reference inhibitor. In the end, we can only make a statement as to whether the test substance enters the cell through the specific transporter if we use the test substance instead of the reference inhibitors and also measure a reduction in CLF uptake.

The model can also be used to look at the extent to which two drugs may compete with each other for the transporter, i.e., whether it comes to drug-drug interactions, in which a drug can prevent another from being taken up in the liver cell.
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You have reached this page because you might be interested in the following topic areas:
Sodium salt, pauli magnus, intestine absorption, liver disease. You might ber also interested inatp binding cassette abc, amino acids, salt export pump bsep, or drug induced liver injury. INaddition, the themes benign recurrent intrahepatic cholestasis, bile acid transporters, saltexport pump abcb11, hepg2 cells, human bsep, m ight be important as well as familialintrahepatic cholestasis type, export pump bsep abcb11, sodium dependent, bile acids,progressive familial intrahepatic cholestasis and neutral amino acid transport.