Hepatocyte uptake and biliary excretion transport systems (Hepatic Transport Systems)

Hepatocyte uptake and biliary excretion transport systems comprise a coordinated network of membrane proteins located on the sinusoidal and canalicular membranes of hepatocytes. These systems, primarily belonging to the Solute Carrier (SLC) and ATP-Binding Cassette (ABC) superfamilies, are responsible for the hepatic extraction of endogenous compounds like bile acids and bilirubin, as well as the clearance of xenobiotics and drugs (Giacomini et al., 2010, PMID: 20168317). Key uptake transporters include Organic Anion Transporting Polypeptides (OATP1B1, OATP1B3) and the Sodium/Taurocholate Cotransporting Polypeptide (NTCP), while efflux is mediated by the Bile Salt Export Pump (BSEP) and Multidrug Resistance-associated Proteins (MRP2) (Kalliokoski & Niemi, 2009, PMID: 19759158). Dysregulation or inhibition of these transporters can lead to cholestasis, hyperbilirubinemia, and significant drug-drug interactions, making them a critical focus in drug development and safety assessment (Zamek-Gliszczynski et al., 2018, PMID: 30056286). Furthermore, specific transporters like NTCP serve as entry receptors for viruses such as Hepatitis B and D, highlighting their role as direct therapeutic targets for drugs like bulevirtide (Yan et al., 2012, PMID: 23144477). The interplay between these uptake and efflux mechanisms determines the intracellular concentration of drugs, influencing both therapeutic efficacy and the risk of hepatotoxicity (Stieger, 2011, PMID: 21295118). Consequently, these systems are extensively studied during preclinical drug development to predict human pharmacokinetics and potential adverse effects.

Other names

Hepatic transportersHepatobiliary transport systemSinusoidal and canalicular transportersLiver transport systemsHepatobiliary transporters

Drugs interact with these systems by acting as substrates, inhibitors, or inducers of specific sinusoidal uptake transporters (e.g., OATPs, NTCP) and canalicular efflux transporters (e.g., BSEP, MRP2, MDR1). Therapeutic mechanisms include blocking viral entry (e.g., NTCP inhibition by bulevirtide), while adverse mechanisms involve the inhibition of bile acid transport (e.g., BSEP inhibition) leading to cholestasis or the competition for uptake/efflux sites resulting in altered drug pharmacokinetics and drug-drug interactions (Giacomini et al., 2010, PMID: 20168317; Zamek-Gliszczynski et al., 2018, PMID: 30056286).