A novel transcellular transport pathway for non-bile salt cholephilic organic anions

Aoyama, Nankei; Tokumo, Hironori; Ohya, Toshihide; Chandler, Kimberly; Holzbach, Rüdiger

doi:10.1152/ajpgi.1991.261.2.g305

Cited by 7 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The hydrophobicity of the compound influences which pathway the solute will take. The more hydrophobic the solute the more it will associate with intracellular membranes rather than the cytosolic proteins (30, 225). …”

Section: Cellular and Molecular Determinants Of Bile Formationmentioning

confidence: 99%

Bile Formation and Secretion

Boyer

2013

Comprehensive Physiology

681

602

View full text Add to dashboard Cite

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.

show abstract

Section: Cellular and Molecular Determinants Of Bile Formationmentioning

confidence: 99%

Bile Formation and Secretion

Boyer

2013

Comprehensive Physiology

681

602

View full text Add to dashboard Cite

show abstract

“…ICG is useful in studies of transcellular transport because it is not metabolized. Transcellular transport may follow different routes: passive diffusion in the cytosol of ligandprotein complex, transport mediated by intracellular membrane structures, vesicular microfilament dependent transport (inhibited by colchicin), and transport mediated via the Golgi apparatus (inhibited by monensin) (Aoyama et al 1991b;Aoyama et al 1991b). The paracellular pathway appears only to transport organic cations (Meijer & Groothuis 1991).…”

Section: Tkansport Of Icg Through the Hepatocytementioning

confidence: 99%

Hepatic Elimination of Indocyanine Green with Special Reference to Distribution Kinetics and the Influence of Plasma Protein Binding

Ott

1998

Pharmacology & Toxicology

View full text Add to dashboard Cite

“…Hydrophobic molecules take longer to reach the bile than binding of palmitate to membranes. Because the soluble fraction is more motheir more hydrophilic brethren, 97 presumably reflecting bile, binding proteins increase cytoplasmic mobility. Data have been replotted from their original sources 4,100 .…”

Section: Fraction Cytoplasmic Binding Proteins Increase the Soluble mentioning

confidence: 99%

When is a carrier not a membrane carrier? The cytoplasmic transport of amphipathic molecules

Weisiger¹

1996

Hepatology

View full text Add to dashboard Cite

lular water layers. This article reviews how this process After entering the cell, small molecules must penetrate works and how it may fail in certain disease states. the cytoplasm before they are metabolized, excreted, or can convey information to the cell nucleus. Without effi-THE VARIETY OF SOLUBLE BINDING PROTEINS cient cytoplasmic transport, most such molecules would efflux back out of the cell before they could reach their Many biologically important compounds are only sparingly targets. Cytoplasmic movement of amphipathic mole-soluble in water. For example, the solubility of long-chain cules (e.g., long-chain fatty acids, bilirubin, bile acids) is fatty acids at physiological pH is õ10 mmol/L, 7,8 while that greatly slowed by their tendency to bind intracellular of bilirubin is õ1 nmol/L. 9,10 Other metabolites with low solustructures. Soluble cytoplasmic binding proteins reduce bilities include phospholipids, 11 hydrophobic bile acids, 12 retithis binding by increasing the aqueous solubility of their noids, 13 coenzyme A-esters, 14 cholesterol, 15 thyroid and steligands. These soluble carriers catalyze the transport of roid hormones, 16 and a wide variety of exogenous drugs and hydrophobic molecules across hydrophilic water layers, toxins collectively termed ''organic anions.'' Solubility of these just as membrane carriers catalyze the transport of hy-molecules may be greatly increased by binding proteins. drophilic molecules across the hydrophobic membrane These proteins provide mobile hydrophobic binding sites that core. They even display the kinetic features of carrier-allow amphipathic molecules to penetrate into and across mediated transport, including saturation, mutual com-aqueous layers that would otherwise block transport. 17 This petition between similar molecules, and countertrans-function has been compared with boats (the binding proteins) port. Recent data suggest that amphipathic molecules carrying nonswimming passengers (the amphipaths) across cross the cytoplasm very slowly, with apparent diffusion a river (the water layer). 18 Cytoplasm contains a large numconstants 10 2 to 10 4 times smaller than in water. By mod-ber of soluble binding proteins. These include fatty acid bindulating the rate of cytoplasmic transport, cytosolic bind-ing proteins, 19 of glutathione S-transferases with overlapping specificities. 26 Albumin serves a similar function outside the cell by carrying long chain fatty acids and numerous organic anions across The oldest paradigm in transport physiology is that cell unstirred plasma layers near the cell surface. 17 membranes provide the major barrier to cellular uptake and secretion. This is clearly true for hydrophilic molecules such

show abstract

A novel transcellular transport pathway for non-bile salt cholephilic organic anions

Cited by 7 publications

References 0 publications

Bile Formation and Secretion

Bile Formation and Secretion

Hepatic Elimination of Indocyanine Green with Special Reference to Distribution Kinetics and the Influence of Plasma Protein Binding

When is a carrier not a membrane carrier? The cytoplasmic transport of amphipathic molecules

Contact Info

Product

Resources

About