Bile acid transporters (BATs)

Bile acid transporters are a group of specialized proteins responsible for the movement of bile acids across cellular membranes, primarily within the liver and intestines. They play a critical role in the enterohepatic circulation, a process that recycles approximately 95% of bile acids to maintain homeostasis and facilitate the absorption of dietary fats and fat-soluble vitamins (StatPearls, 2023). Key members include the Apical Sodium-dependent Bile Acid Transporter (ASBT/SLC10A2) in the ileum and the Na+/taurocholate cotransporting polypeptide (NTCP/SLC10A1) in the liver (UniProt, 2024). Dysregulation of these transporters is linked to various cholestatic liver diseases, where the accumulation of toxic bile acids causes liver injury and severe pruritus (PubMed, 2022). Pharmacological inhibition of ASBT has emerged as a therapeutic strategy to lower systemic bile acid levels in conditions like Alagille syndrome and progressive familial intrahepatic cholestasis (PFIC) (FDA, 2021). Additionally, NTCP serves as the entry receptor for Hepatitis B and D viruses, making it a target for antiviral therapies like bulevirtide (Journal of Hepatology, 2023). Other transporters in this class, such as the Bile Salt Export Pump (BSEP), are essential for secreting bile from hepatocytes into the bile canaliculi (Nature Reviews Gastroenterology & Hepatology, 2021). Therapeutic agents targeting these proteins aim to either interrupt the bile acid cycle to treat metabolic and cholestatic disorders or block viral infection pathways.

Other names

Bile acid transport proteinsSolute carrier family 10SLC10 familyIleal bile acid transporterIBATApical sodium-dependent bile acid transporterASBTNa+/taurocholate cotransporting polypeptideNTCPBile salt export pumpBSEPOrganic solute transporter alpha/betaOST-alpha/beta

Drugs targeting bile acid transporters primarily act by inhibiting the reabsorption of bile acids in the ileum (ASBT inhibitors) or blocking their uptake into hepatocytes (NTCP inhibitors). ASBT inhibitors, such as maralixibat and odevixibat, prevent the recycling of bile acids, leading to increased fecal excretion and a reduction in the systemic bile acid pool, which alleviates cholestatic symptoms like pruritus. NTCP inhibitors, such as bulevirtide, competitively bind to the transporter to prevent the entry of Hepatitis B and D viruses into liver cells.