Bile acid transporters in health and disease

Abstract

In recent years the discovery of a number of major transporter proteins expressed in the liver and intestine specifically involved in bile acid transport has led to improved understanding of bile acid homeostasis and the enterohepatic circulation. Sodium (Na⁺)-dependent bile acid uptake from portal blood into the liver is mediated primarily by the Na⁺ taurocholate co-transporting polypeptide (NTCP), while secretion across the canalicular membrane into the bile is carried out by the bile salt export pump (BSEP). In the ileum, absorption of bile acids from the lumen into epithelial cells is mediated by the apical Na⁺ bile salt transporter (ASBT), whereas exit into portal blood across the basolateral membrane is mediated by the organic solute transporter α/β (OSTα/β) heterodimer. Regulation of transporter gene expression and function occurs at several different levels: in the nucleus, members of the nuclear receptor superfamily, regulated by bile acids and other ligands are primarily involved in controlling gene expression, while cell signalling events directly affect transporter function, and subcellular localization. Polymorphisms, dysfunction, and impaired adaptive responses of several of the bile acid transporters, e.g. BSEP and ASBT, results in liver and intestinal disease. Bile acid transporters are now understood to play central roles in driving bile flow, as well as adaptation to various pathological conditions, with complex regulation of activity and function in the nucleus, cytoplasm, and membrane.

Keywords :

• Transporters
• bile acids
• liver
• regulation
• nuclear receptors