Mechanisms of Bile Secretion and Hepatic Transport

Boyer, James L.

doi:10.1007/978-1-4613-2097-5_35

Cited by 38 publications

(21 citation statements)

References 234 publications

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“…Bile is a highly complex secretion which is aqueous in nature and contains less than 5% solid contents in most species (86). Bile cannot be sampled at its origin for obvious anatomical reasons but is isoosmotic with respect to plasma when collected from the bile ducts.…”

Section: Components Of Bilementioning

confidence: 99%

“…Their concentrations range from 140 to 810mg/dL and 97 to 320 mg/dL, respectively (73). PC accounts for nearly all biliary phospholipids in bile even though the canalicular membrane also contains sphingomyelin, phosphatidylethanolamine, and phosphatidylserine (427).…”

Section: Transport and Excretion Of Specific Substancesmentioning

confidence: 99%

“…Acidic and sulfur-containing amino acids are present in mmol/L amounts in bile (73). The tripeptide GSH is a major biliary peptide whose secretion by Mrp2 represents the principle determinant of canalicular BSIF (48).…”

Section: Transport and Excretion Of Specific Substancesmentioning

confidence: 99%

“…Metals are normally complexed with amino acids, peptides, proteins, and other tissue constituents and usually do not exist in free solution. A few metals like Ca 2+ and Mg 2+ which are similar in concentration in blood plasma and bile, may enter bile by a paracellular pathway by diffusion across the tight junctions (73). A P-type ATPase, ATP7B, is required for the biliary excretion of copper and is mutated in Wilson’s disease (98, 217, 345, 465, 544).…”

Section: Transport and Excretion Of Specific Substancesmentioning

confidence: 99%

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Bile Formation and Secretion

Boyer

2013

Comprehensive Physiology

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681

602

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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.

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Section: Components Of Bilementioning

confidence: 99%

Section: Transport and Excretion Of Specific Substancesmentioning

confidence: 99%

Section: Transport and Excretion Of Specific Substancesmentioning

confidence: 99%

Section: Transport and Excretion Of Specific Substancesmentioning

confidence: 99%

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Bile Formation and Secretion

Boyer

2013

Comprehensive Physiology

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681

602

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“…This pathway delivers newly synthesized proteins to the blood and involves fusion of camer vesicles with the basolateral plasma membrane (PM). Transport of proteins into bile, mediated by fusion of vesicles with the apical PM, is by transcytosis rather than by direct traffic from the Golgi complex (2).…”

mentioning

confidence: 99%

Exocytic transport vesicles generated in vitro from the trans-Golgi network carry secretory and plasma membrane proteins.

Salamero¹,

Sztul²,

Howell³

1990

Proc. Natl. Acad. Sci. U.S.A.

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We have developed a cell-free assay that reproduces vesicular budding during exit from the Golgi complex. The starting preparation for the in vitro system was a rat liver stacked Golgi fraction immobilized on a magnetic solid support by means of an antibody against the cytoplasmic domain of the polymeric IgA receptor. Vesicular budding was ATP, cytosol, and temperature dependent and was inhibited by 1 mMN-ethylmaleimide. Budding was maximum within 10 min and originated preferentially from the trans-Golgi. Exocytic transport vesicles immunoisolated from the total budded population were enriched in the mature forms of secretory and membrane proteins destined to the basolateral plasma membrane and were depleted in lysosomal enzymes and galactosyltransferase activity. The finding that a major proportion (>70%) of newly synthesized, sialylated secretory and transmembrane proteins is contained in a single population of post-Golgi transport vesicles implies that, in a constitutively secreting cell, basolaterally destined proteins are sorted and packaged together into the same exocytic transport vesicles.The hepatocyte, a polarized epithelial cell, lacks storage granules or a known secretagogue, indicating that in this cell only a constitutive secretory pathway exists (1). This pathway delivers newly synthesized proteins to the blood and involves fusion of camer vesicles with the basolateral plasma membrane (PM). Transport of proteins into bile, mediated by fusion of vesicles with the apical PM, is by transcytosis rather than by direct traffic from the Golgi complex (2).Traffic of hepatocyte PM proteins seems to parallel that of secretory proteins. Bartles et al. (3) have presented evidence that PM proteins are initially transported to the basolateral PM, irrespective of their ultimate destination to either the basolateral or the apical PM. However, recent data suggest that sorting of apical and basolateral PM proteins can take place either intracellularly, at the trans-Golgi network (TGN), or at the basolateral PM depending on the protein and the cell type (4-6).Although it is likely that in constitutively secreting cells, PM and secretory proteins are transported from the Golgi to the cell surface in the same transport vesicles, there is currently no direct evidence for this in mammalian cells. Previous electron microscopic studies in hepatoma cells (7) indicated that a secretory protein (albumin) and a viral trans-membrane protein destined to the PM colocalize in structures within the Golgi region, some of which could represent exocytic transport vesicles.Several defined steps of biosynthetic protein traffic have been reconstituted in cell-free assays. Transport from the endoplasmic reticulum to the Golgi complex (8), between compartments of the Golgi complex (9), and from the Golgi complex to the plasma membrane (10, 11) has been investigated. In all of these studies the reporter molecules followed were viral proteins. We have designed a cell-free system that reconstitutes the formation and release of trans...

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Measurement of Hepatobiliary Transport

Ballatori

2004

CP Toxicology

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A major hepatic function involves the removal of xenobiotics from portal blood and their subsequent storage, metabolism, and excretion into bile, or delivery of various products back into the bloodstream. Transport across the liver cell basolateral (or sinusoidal) plasma membrane is a key step in the overall metabolism of many compounds, whereas transport across the apical (or canalicular) plasma membrane into bile is often the principal pathway for their elimination. Although significant progress has been made in the molecular identification of the transport proteins that mediate these processes, much remains to be learned about regulation and physiological integration. The critical limiting factor in studying biliary excretion is that the bile canaliculus is very small (~1 µm in diameter) and is generally inaccessible to sampling by conventional approaches. The bile canalicular membrane is a specialized part of the hepatocellular plasma membrane, such that bile is separated from blood plasma only by the tight junctions that encircle each hepatocyte. Because hepatocyte polarity is rapidly lost during cell isolation, most cell culture models provide only limited information on mechanisms of biliary excretion. Thus, biliary secretion has been studied using four major experimental models: canalicular plasma membrane vesicles, cultured hepatocyte couplets, perfused liver, and in vivo (bile duct-cannulated animals). This unit describes basic methods for collecting bile from anesthetized mice and rats, for carrying out isolated perfused rat liver studies, and for the simultaneous isolation of plasma membrane vesicles derived from the basolateral and canalicular domains of rat liver.

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Mechanisms of Bile Secretion and Hepatic Transport

Cited by 38 publications

References 234 publications

Bile Formation and Secretion

Bile Formation and Secretion

Exocytic transport vesicles generated in vitro from the trans-Golgi network carry secretory and plasma membrane proteins.

Measurement of Hepatobiliary Transport

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