Bile Formation and Secretion

Abstract

Bile is a unique and vital aqueous secretion of the liver that is formed by the hepatocyte and modified down stream by absorptive and secretory properties of the bile duct epithelium. Approximately 5% of bile consists of organic and inorganic solutes of considerable complexity. The bile-secretory unit consists of a canalicular network which is formed by the apical membrane of adjacent hepatocytes and sealed by tight junctions. The bile canaliculi (~1 μm in diameter) conduct the flow of bile countercurrent to the direction of portal blood flow and connect with the canal of Hering and bile ducts which progressively increase in diameter and complexity prior to the entry of bile into the gallbladder, common bile duct, and intestine. Canalicular bile secretion is determined by both bile salt-dependent and independent transport systems which are localized at the apical membrane of the hepatocyte and largely consist of a series of adenosine triphosphate-binding cassette transport proteins that function as export pumps for bile salts and other organic solutes. These transporters create osmotic gradients within the bile canalicular lumen that provide the driving force for movement of fluid into the lumen via aquaporins. Species vary with respect to the relative amounts of bile salt-dependent and independent canalicular flow and cholangiocyte secretion which is highly regulated by hormones, second messengers, and signal transduction pathways. Most determinants of bile secretion are now characterized at the molecular level in animal models and in man. Genetic mutations serve to illuminate many of their functions.

Expression of mediators of purinergic signaling in human liver cell lines

“…Myofibroblasts derived from HSC are the primary effector cells in liver fibrosis [49][50][51], whereas hepatocytes and cholangiocytes work in coordinated fashion to secrete bile [52] and are primary targets of a variety of liver diseases [53,54] . Isolation of HSC, hepatocytes, and cholangiocytes is now technically straightforward [55], yet there are good reasons to use cell culture models of each of these cell types.…”

Role of Multidrug Resistance Protein 3 in Antifungal-Induced Cholestasis

“…Primary bile is formed at the canalicular membrane of hepatocytes in a process that requires the interplay of several ATPbinding cassette transporters. In addition to small solutes, the main components of primary bile are bile salt (BS), phosphatidylcholine (PC), and cholesterol (Boyer, 2013). The BS export pump (BSEP, protein name; ABCB11, gene name) mediates ATP-dependent transport of BS from hepatocytes into the canaliculus.…”

Partial Ligation of the Common Bile Duct Results in Reversible Cholestasis in Rats

“…9 To investigate the adaptive response of bile transporter expression to PBDL, the mRNA and protein expression levels of Ntcp and Bsep was examined. Ntcp and Bsep gene expression, quantified by qRT-PCR, were significantly decreased in the PBDL group compared with the sham group; however, a tendency to recover was observed (Fig.…”