Hepatobiliary bile acid transport system

The hepatobiliary bile acid transport system is a coordinated network of membrane proteins and regulatory factors responsible for the uptake, intracellular transport, and canalicular secretion of bile acids and other cholephilic compounds [1.1.1, 1.2.1]. Key components include basolateral uptake transporters like the Sodium/taurocholate cotransporting polypeptide (NTCP) and canalicular efflux pumps such as the Bile salt export pump (BSEP) and Multidrug resistance-associated protein 2 (MRP2) [1.1.3, 1.3.4]. This machinery is essential for maintaining bile flow, facilitating the absorption of dietary lipids, and eliminating metabolic waste and xenobiotics from the body [1.1.1, 1.2.3]. Dysregulation or genetic mutations in these transporters lead to cholestasis, a condition characterized by the accumulation of toxic bile acids within hepatocytes, resulting in liver injury, fibrosis, and cirrhosis [1.1.2, 1.2.2]. Therapeutic strategies often target this system through nuclear receptors like the Farnesoid X receptor (FXR) to modulate transporter expression or by inhibiting intestinal reabsorption to reduce the total bile acid pool [1.3.1, 1.3.5]. Monitoring efficacy and safety typically involves measuring serum bile acids and liver enzymes such as alkaline phosphatase [1.3.1].

Other names

Hepatobiliary bile acid transporters and cholestasis-related bile secretory machineryBile acid transport systemHepatobiliary secretory machineryBile acid transportersSodium/taurocholate cotransporting polypeptide (NTCP)Bile salt export pump (BSEP)Multidrug resistance-associated protein 2 (MRP2)Multidrug resistance protein 3 (MDR3)Farnesoid X receptor (FXR)

Agonism of the Farnesoid X receptor (FXR) to downregulate bile acid uptake and synthesis while upregulating efflux; inhibition of the apical sodium-dependent bile acid transporter (ASBT) to reduce enterohepatic circulation; induction of alternative basolateral efflux pathways; and direct inhibition of the bile salt export pump (BSEP) as a toxicological mechanism.