scholarly journals Partial characterization of regulation of biliary lecithin hydrophobicity: association with organic anion-induced solute cholestasis in rats

1995 ◽  
Vol 312 (3) ◽  
pp. 795-797 ◽  
Author(s):  
H Miura ◽  
S Tazuma ◽  
G Kajiyama
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Organic Anion ◽  
Sodium Taurocholate ◽  
Biliary Secretion ◽  
Acid Ratio ◽  
Constant Rate ◽  
Phospholipid Ratio ◽  
Bile Salt Micelle

We examined the effects of the depletion of bile salts and of the intravenous infusion of sodium taurocholate (STC) with or without bromosulphophthalein (BSP) in rats on the biliary secretion of lipids to clarify the regulatory mechanism(s). Each rat was equipped with a bile-duct cannula to collect bile. After the endogenous bile salt pool was depleted, STC was infused at a constant rate (160 nmol/min per 100 g body wt.) with or without BSP (50, 100, or 150 nmol/min per 100 g body wt.). BSP reduced the biliary secretion of cholesterol and phospholipids dose-dependently without affecting the secretion of bile salts (uncoupling phenomenon). Compared with the physiological and STC-infused condition, the biliary cholesterol/phospholipid ratio and saturated/unsaturated fatty acid ratio increased under the bile salts depletion and uncoupling phenomenon. Data indicate that the hydrophobicity of biliary lecithin increases with a decrease in the bile salt micelle capacity to induce biliary lipid secretion, resulting in a higher packing density of biliary vesicle. The cholesterol-holding capacity of the biliary vesicle is therefore enhanced during the depletion of bile salts and the uncoupling phenomenon.

Effect of glycodihydrofuisidate on sulfobromophthalein transport maximum in the hamster

1976 ◽  
Vol 231 (6) ◽  
pp. 1875-1878 ◽  
Author(s):  
Y Delage ◽  
M Dumont ◽  
S Erlinger
Keyword(s):  
Bile Salt ◽  
Transport System ◽  
Bile Salts ◽  
Sodium Taurocholate ◽  
Specific Effect ◽  
Biliary Secretion ◽  
Biliary Lipid ◽  
Lipid Secretion ◽  
Dye Transport ◽  
Cholesterol Secretion

The effect on sulfobromophathalein transport maximum (Tm) and biliary lipid secretion of sodium glyco-24,25-dihydrofusicate, a micelle-forming compound secreted into bile, has been studied in the hamster and compared to that of a physiological bile salt, sodium taurocholate. Biliary phospholipid and cholesterol secretion increased both during glycodihydrofusidate and taurocholate administration, an observation which suggest that both compounds increased th biliary secretion of micelle-forming compounds. In contrast, only taurocholate increased sulfobromophthalein Tm into bile, while glycodihydrofusidate administration decreased it. This observation suggests that the increase in sulfobromophthalein Tm observed during taurocholate administration is not the result of micellar sequestration. It could rather be the consequence of a specific effect of bile salts on the dye transport system.

scholarly journals Characteristics of bile salt uptake into skate hepatocytes

1994 ◽  
Vol 299 (3) ◽  
pp. 665-670 ◽  
Author(s):  
G Fricker ◽  
V Dubost ◽  
K Finsterwald ◽  
J L Boyer
Keyword(s):  
Substrate Specificity ◽  
Bile Salt ◽  
Transport System ◽  
Bile Salts ◽  
Organic Anion ◽  
Anion Transport ◽  
Organic Anion Transport ◽  
Salt Uptake ◽  
Anion Transport System ◽  
Alpha 7

The substrate specificity for the transporter that mediates the hepatic uptake of organic anions in freshly isolated hepatocytes of the elasmobranch little skate (Raja erinacea) was determined for bile salts and bile alcohols. The Na(+)-independent transport system exhibits a substrate specificity, which is different from the specificity of Na(+)-dependent bile salt transport in mammals. Unconjugated and conjugated di- and tri-hydroxylated bile salts inhibit uptake of cholyltaurine and cholate competitively. Inhibition is significantly greater with unconjugated as opposed to glycine- or taurine-conjugated bile salts. However, the number of hydroxyl groups in the steroid moiety of the bile salts has only minor influences on the inhibition by the unconjugated bile salts. Since the transport system seems to represent an archaic organic-anion transport system, other anions, such as dicarboxylates, amino acids and sulphate, were also tested, but had no inhibitory effect on bile salt uptake. To clarify whether bile alcohols, the physiological solutes in skate bile, share this transport system, cholyltaurine transport was studied after addition of 5 beta-cholestane-3 beta,5 alpha,6 beta-triol, 5 alpha-cholestan-3 beta-ol and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. These bile alcohols inhibit cholyltaurine uptake non-competitively. In contrast, uptake of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol, which is Na(+)-independent, is not inhibited by cholyltaurine. The findings further characterize a Na(+)-independent organic-anion transport system in skate liver cells, which is not shared by bile alcohols and has preference for unconjugated lipophilic bile salts.

Effect of intestinal resection on bile salt absorption in dogs

1965 ◽  
Vol 208 (2) ◽  
pp. 363-369 ◽  
Author(s):  
M. R. Playoust ◽  
Leon Lack ◽  
I. M. Weiner
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Enterohepatic Circulation ◽  
Sodium Taurocholate ◽  
Intestinal Resection ◽  
High Fat ◽  
Salt Absorption ◽  
Complete Failure ◽  
Fat Meal

The efficiency of intestinal absorption of bile salts was evaluated by studying the rate of disappearance of radioactivity from the bile of dogs after the intravenous administration of sodium taurocholate-24-C14. Bile was sampled through an indwelling tube in the gall bladder. One day after a high-fat meal normal dogs retained 48% of the radioactivity; dogs with resection of the jejunum retained 48%, whereas those with resection of the ileum retained only 3% in the bile. This is consistent with previous observations that the ileum is the site of bile salt absorption in vitro and in anesthetized animals. Animals with resection of the ileum exhibited significant steatorrhea; however, three-fourths of the ingested fat was absorbed in spite of almost complete failure to absorb bile salts. This indicates that fat and bile salts are not normally absorbed together. Elimination of enterohepatic circulation of bile salts by resection of the ileum contributes to the observed steatorrhea.

Bile Salt Transporters: Molecular Characterization, Function, and Regulation

2003 ◽  
Vol 83 (2) ◽  
pp. 633-671 ◽  
Author(s):  
Michael Trauner ◽  
James L. Boyer
Keyword(s):  
Bile Salt ◽  
Molecular Characterization ◽  
Bile Salts ◽  
Organic Anion ◽  
Transport Proteins ◽  
Salt Transport ◽  
Transport Systems ◽  
Cholestatic Liver Disease ◽  
Bile Salt Transporters ◽  
Bile Salt Transport

Molecular medicine has led to rapid advances in the characterization of hepatobiliary transport systems that determine the uptake and excretion of bile salts and other biliary constituents in the liver and extrahepatic tissues. The bile salt pool undergoes an enterohepatic circulation that is regulated by distinct bile salt transport proteins, including the canalicular bile salt export pump BSEP (ABCB11), the ileal Na+-dependent bile salt transporter ISBT (SLC10A2), and the hepatic sinusoidal Na+- taurocholate cotransporting polypeptide NTCP (SLC10A1). Other bile salt transporters include the organic anion transporting polypeptides OATPs (SLC21A) and the multidrug resistance-associated proteins 2 and 3 MRP2,3 (ABCC2,3). Bile salt transporters are also present in cholangiocytes, the renal proximal tubule, and the placenta. Expression of these transport proteins is regulated by both transcriptional and posttranscriptional events, with the former involving nuclear hormone receptors where bile salts function as specific ligands. During bile secretory failure (cholestasis), bile salt transport proteins undergo adaptive responses that serve to protect the liver from bile salt retention and which facilitate extrahepatic routes of bile salt excretion. This review is a comprehensive summary of current knowledge of the molecular characterization, function, and regulation of bile salt transporters in normal physiology and in cholestatic liver disease and liver regeneration.

How does bile salt penetration affect the self-assembled architecture of pluronic P123 micelles? – light scattering and spectroscopic investigations

2015 ◽  
Vol 17 (30) ◽  
pp. 19977-19990 ◽  
Author(s):  
Arpita Roy ◽  
Niloy Kundu ◽  
Debasis Banik ◽  
Jagannath Kuchlyan ◽  
Nilmoni Sarkar
Keyword(s):  
Light Scattering ◽  
Bile Salt ◽  
Bile Salts ◽  
Triblock Copolymer ◽  
Sodium Taurocholate ◽  
Sodium Deoxycholate ◽  
The Self ◽  
Spectroscopic Investigations ◽  
Pluronic P123 ◽  
Supramolecular Aggregate

The triblock copolymer of the type (PEO)20–(PPO)70–(PEO)20 (P123) forms a mixed supramolecular aggregate with different bile salts, sodium deoxycholate (NaDC) and sodium taurocholate (NaTC), having different hydrophobicity.

scholarly journals Partial characterization of mechanism(s) by which sulphobromophthalein reduces biliary lipid secretion

1993 ◽  
Vol 291 (1) ◽  
pp. 173-177 ◽  
Author(s):  
G Yamashita ◽  
S Tazuma ◽  
K Horikawa ◽  
N Aihara ◽  
H Ochi ◽  
...  
Keyword(s):  
Bile Salt ◽  
Sodium Taurocholate ◽  
Bile Canaliculus ◽  
Biliary Secretion ◽  
Dependent Manner ◽  
Biliary Lipid ◽  
Sprague Dawley ◽  
Lipid Secretion ◽  
Biliary Lipids ◽  
Sprague Dawley Rats

This study was performed to explore the mechanisms by which sulphobromophthalein (BSP) reduces the secretion of biliary lipid using Sprague-Dawley rats (SDR) and mutant rats with congenital conjugated hyperbilirubinaemia bred from SDR (EHBR). We infused the bile-salt-pool-depleted rats with sodium taurocholate at a constant rate of 160 nmol/min per 100 g body wt. with BSP (12.5, 25 and 50 nmol/min per 100 g body wt.) or BSP-GSH (12.5, 25 and 50 nmol/min per 100 g body wt.). The biliary secretion of BSP and BSP-GSH was markedly impaired in EHBR as compared with that in SDR. BSP reduced the biliary secretion of cholesterol and phospholipids in a dose-dependent manner without affecting the secretion of bile salts and composition of fatty acids in phospholipids in SDR, but had no effect on lipid secretion in EHBR. In contrast, BSP-GSH had no such effect on biliary lipids, either in the SDR or EHBR. In addition, the amount of BSP in the liver of EHBR was in the same range as that of SDR. Therefore it is unlikely that an intracellular mechanism is involved in the phenomenon of uncoupling by BSP. We conclude that the uncoupling of biliary lipids from bile-salt secretion by BSP occurs at the level of the bile canaliculus following the secretion of unconjugated BSP.

scholarly journals Pathophysiological basis of liver disease in cystic fibrosis employing a ΔF508 mouse model

2008 ◽  
Vol 294 (6) ◽  
pp. G1411-G1420 ◽  
Author(s):  
Folke Freudenberg ◽  
Annemarie L. Broderick ◽  
Bian B. Yu ◽  
Monika R. Leonard ◽  
Jonathan N. Glickman ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Liver Disease ◽  
Bile Acid ◽  
Mouse Model ◽  
Bile Salt ◽  
Bile Salts ◽  
Divalent Metal ◽  
Unconjugated Bilirubin ◽  
Fecal Bile Acid ◽  
Phospholipid Ratio

The molecular pathogenesis of cystic fibrosis (CF) liver disease is unknown. This study investigates its earliest pathophysiological manifestations employing a mouse model carrying ΔF508, the commonest human CF mutation. We hypothesized that, if increased bile salt spillage into the colon occurs as in the human disease, then this should lead to a hydrophobic bile salt profile and to “hyperbilirubinbilia” because of induced enterohepatic cycling of unconjugated bilirubin. Hyperbilirubinbilia may then lead to an increased bile salt-to-phospholipid ratio in bile and, following hydrolysis, precipitation of divalent metal salts of unconjugated bilirubin. We document in CF mice elevated fecal bile acid excretion and biliary secretion of more hydrophobic bile salts compared with control wild-type mice. Biliary secretion rates of bilirubin monoglucuronosides, bile salts, phospholipids, and cholesterol are increased significantly with an augmented bile salt-to-phospholipid ratio. Quantitative histopathology of CF livers displays mild early cholangiopathy in ≈53% of mice and multifocal divalent metal salt deposition in cholangiocytes. We conclude that increased fecal bile acid loss leads to more hydrophobic bile salts in hepatic bile and to hyperbilirubinbilia, a major contributor in augmenting the bile salt-to-phospholipid ratio and endogenous β-glucuronidase hydrolysis of bilirubin glucuronosides. The confluence of these perturbations damages intrahepatic bile ducts and facilitates entrance of unconjugated bilirubin into cholangiocytes. This study of the earliest stages of CF liver disease provides a framework for investigating the molecular pathophysiology of more advanced disease in murine models and in humans with CF.

scholarly journals Spectrophotometric determination of the critical micellar concentration of bile salts using bilirubin monoglucuronide as a micellar probe. Utility of derivative spectroscopy

1988 ◽  
Vol 252 (1) ◽  
pp. 275-281 ◽  
Author(s):  
W Spivak ◽  
C Morrison ◽  
D Devinuto ◽  
W Yuey
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Sodium Taurocholate ◽  
Critical Micellar Concentration ◽  
Relative Energy ◽  
Bile Pigment ◽  
Sharp Change ◽  
Derivative Spectroscopy ◽  
Invasive Method ◽  
Sudden Decrease

We have developed a simple biologically non-invasive method for determining the critical micellar concentration (CMC) of bile salts using pure naturally occurring bilirubin IX alpha monoglucuronide (BMG), an important bile pigment present in virtually all mammalian biles. This methodology employs visible absorbance spectroscopy of BMG in bile salts over a range of bile salt concentrations that include the reported CMC. Using 100 microM-BMG in 0.4 M-imidazole buffer at pH 7.8, we calculated that the CMC for sodium taurochenodeoxycholate is between 2.5 and 3.0 mM based on: (1) an abrupt change in lambda max. in this concentration range, (2) a precipitous decrease in the amplitude of the absorbance shoulder at 450 nm, (3) a sudden decrease in the second derivative absorbance of BMG at 400 nm and an increase in absorbance at 470 nm, (4) a sharp change in the 4th derivative absorbance at 375 and 395 nm. In contrast, sodium taurocholate, a bile salt that reportedly does not have a CMC but continuously self-associates over a wide concentration range, exhibited none of these changes. The use of derivative spectroscopy enhances the ability to detect the CMC changes and also indicates the number of BMG species in solution and their relative energy states.

Ileal transposition into the upper jejunum affects lipid and bile salt absorption in rats

1996 ◽  
Vol 271 (4) ◽  
pp. G681-G691 ◽  
Author(s):  
T. Tsuchiya ◽  
T. J. Kalogeris ◽  
P. Tso
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Sodium Taurocholate ◽  
Cholesterol Absorption ◽  
Lymphatic Transport ◽  
Proximal Jejunum ◽  
Ileal Transposition ◽  
Sham Surgery ◽  
Salt Absorption ◽  
Lymph Duct

To determine whether ileal transposition affects absorption and transport of lipids and bile salts, we studied the absorption and lymphatic transport of triglyceride, cholesterol, and sodium taurocholate in rats with the distal quarter of their small bowel transposed to the proximal jejunum and in control rats whose intestines were transected and reanastomosed without transposition. Three weeks after transposition or sham surgery, rats were equipped with duodenal or jejunal and intestinal lymph duct cannulas and then given continuous duodenal or jejunal infusions of lipid emulsion containing triolein (40 mumol/h + [3H]triolein) and cholesterol (7.8 mumol/h + [14C]cholesterol) for 8 h. Lymph lipid output was measured; after 8 h of lipid infusion, luminal and mucosal radioactive lipid distribution was also quantified. Transposition had no effect on triglyceride absorption and transport, but cholesterol absorption and transport were both significantly attenuated in the transposed rats. In a separate study we examined whether ileal transposition would alter the kinetics of bile salt absorption. Six weeks after either transposition or sham surgery, rats were given a duodenal bolus injection of 14C-labeled sodium taurocholate mixed in rat bile, and the output of radiolabeled bile salt through a bile fistula was measured. Appearance of radiolabeled taurocholate was gradual in the control rats, peaking at approximately 90 min after administration. Appearance of labeled bile salt was rapid in the transposed rats, peaking within 60 min after administration. In conclusion, ileal transposition has no effect on triglyceride absorption but attenuates cholesterol absorption and transport, possibly by promoting premature absorption of bile salts.

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