The Role of the Sodium-Taurocholate Cotransporting Polypeptide (NTCP) and of the Bile Salt Export Pump (BSEP) in Physiology and Pathophysiology of Bile Formation

Stieger, Bruno

doi:10.1007/978-3-642-14541-4_5

Cited by 243 publications

(270 citation statements)

References 343 publications

(301 reference statements)

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“…For example, NTCP is a secondary active, electrogenic transporter that mediates substrate uptake by utilizing the electrochemical sodium gradient across the basolateral plasma membrane of hepatocytes (Stieger, 2011). This driving force is maintained by the (Na+K)-ATPase, which requires a continuous supply of ATP.…”

Section: Importance Of Transport Mechanismmentioning

confidence: 99%

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The emerging role of transport systems in liver function tests

Stieger

Heger

Graaf

et al. 2012

European Journal of Pharmacology

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Liver function tests are of critical importance for the management of patients with severe or terminal liver disease. They are also used as prognostic tools for planning liver resections. In recent years many transport systems have been identified that also transport substances employed in liver function tests. Such substances include endogenous bilirubin or exogenously administered indocyanine green, agents for magnetic resonance imaging, agents for single photon emission computed tomography or agents for breath tests. The increasing functional and molecular information on the respective transport systems should improve the management and as a result the outcome of patients scheduled for liver surgery or transplantation. To achieve the latter goal, clinical studies that assess individual patients' liver function over the course of their disease with liver function tests are needed to firmly establish and validate recently introduced and novel liver function markers. The emerging role of transport systems in liver function tests Bruno Stieger is supported by grant # 31003A_124652 from the Swiss National Science foundation. AbstractLiver function tests are of critical importance for the management of patients with severe or terminal liver disease. They are also used as prognostic tools for planning liver resections. In recent years many transport systems have been identified, that also transport substances employed in liver function tests. Such substances include endogenous bilirubin or exogenously administered indocyanine green, agents for magnetic resonance imaging, agents for single photon emission computed tomography or agents for breath tests. The increasing functional and molecular information on the respective transport systems should improve the management and as a result the outcome of patients scheduled for liver surgery or transplantation. To achieve the latter goal, clinical studies that assess individual patients liver function over the course of their disease with liver function testes are needed to firmly establish and validate recently introduced and novel liver function markers.

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Section: Importance Of Transport Mechanismmentioning

confidence: 99%

“…J Pharmacol Exp Ther 276, 891-896. Extensive information on the known functional variants of the transporters can be found in (Stieger and Meier, 2011) except for 1 (Kalliokoski and Niemi, 2009) and 2 (Stieger, 2011).…”

Section: Referencesmentioning

confidence: 99%

The emerging role of transport systems in liver function tests

Stieger

Heger

Graaf

et al. 2012

European Journal of Pharmacology

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“…Among these, the sodium taurocholate cotransporter polypeptide (NTCP; SLC10A1) is a major BA uptake transporter in the liver that preferentially moves conjugated BA into mature hepatocytes in a sodium‐dependent manner 3, 4, 5. In humans, NTCP accounts for more than 80% of the hepatic uptake of bile salts (Na + ‐dependent pathway) 6, 7, 8. Alternatively, isoforms of the organic anion transporting polypeptides multispecific transporter family compensate for NTCP deficiency by internalizing conjugated and unconjugated BA (Na + ‐independent pathway) 9, 10.…”

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confidence: 99%

Age‐dependent glycosylation of the sodium taurocholate cotransporter polypeptide: From fetal to adult human livers

Sargiacomo

El-Kehdy

Pourcher

et al. 2018

Hepatology Communications

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Sodium taurocholate cotransporter polypeptide (NTCP), mainly expressed on the sinusoidal membrane of hepatocytes, is one of the major transporters responsible for liver bile acid (BA) re‐uptake. NTCP transports conjugated BA from the blood into hepatocytes and is crucial for correct enterohepatic circulation. Studies have shown that insufficient hepatic clearance of BA correlates with elevated serum BA in infants younger than 1 year of age. In the current study, we investigated human NTCP messenger RNA and protein expression by using reverse‐transcription quantitative polymerase chain reaction and immunoblotting in isolated and cryopreserved human hepatocytes from two different age groups, below and above 1 year of age. Here, we show that NTCP messenger RNA expression is not modulated whereas NTCP protein posttranslational glycosylation is modulated in an age‐dependent manner. These results were confirmed by quantification analysis of NTCP 55‐kDa N‐glycosylated bands, which showed significantly less total NTCP protein in donors below 1 year of age compared to donors older than 1 year. NTCP tissue localization was also analyzed by means of immunofluorescence. This revealed that NTCP cellular localization in fetal samples was mainly perinuclear, suggesting that NTCP is not glycosylated, while its postnatal localization on the plasma membrane is age dependent compared to multidrug resistant protein 2, which is apical starting in fetal life. Conclusion: After birth, the NTCP age‐dependent maturation process requires approximately 1 year to complete NTCP glycosylation in human hepatocytes. Therefore, NTCP late posttranslational glycosylation appears to be important for correct NTCP membrane localization, which might explain physiologic cholestasis in neonatal life and might play a central role for HBV infection after birth. (Hepatology Communications 2018;2:693‐702)

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“…Finally, NTCP, which predominantly transports glycine and taurine conjugated bile salt uptake system, and to a lesser degree also some drugs such as for example rosuvastatin [18].…”

Section: Drug Transporters In the Livermentioning

confidence: 99%

“…The prototypic, endogenous substrates of the enterohepatic circulation are bile salts [16][17][18]. Bile salts are bile acids conjugated with taurine or glycine.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetics of Drug Transporters in the Enterohepatic Circulation

Stieger

Meier

2011

Pharmacogenomics

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This article summarizes the impact of the pharmacogenetics of drug transporters expressed in the enterohepatic circulation on the pharmacokinetics and pharmacodynamics of drugs. The role of pharmacogenetics in the function of drug transporter proteins in vitro is now well established and evidence is rapidly accumulating from in vivo pharmacokinetic studies, which suggests that genetic variants of drug transporter proteins can translate into clinically relevant phenotypes. However, a large amount of conflicting information on the clinical relevance of drug transporter proteins has so far precluded the emergence of a clear picture regarding the role of drug transporter pharmacogenetics in medical practice. This is very well exemplified by the case of P-glycoprotein (MDR1, ABCB1). The challenge is now to develop pharmacogenetic models with sufficient predictive power to allow for translation into drug therapy. This will require a combination of pharmacogenetics of drug transporters, drug metabolism and pharmacodynamics of the respective drugs.

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The Role of the Sodium-Taurocholate Cotransporting Polypeptide (NTCP) and of the Bile Salt Export Pump (BSEP) in Physiology and Pathophysiology of Bile Formation

Cited by 243 publications

References 343 publications

The emerging role of transport systems in liver function tests

The emerging role of transport systems in liver function tests

Age‐dependent glycosylation of the sodium taurocholate cotransporter polypeptide: From fetal to adult human livers

Pharmacogenetics of Drug Transporters in the Enterohepatic Circulation

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