scholarly journals Effects of organic anions on biliary lipid secretion in rats. Importance of association with biliary lipid structures

1992 ◽  
Vol 286 (1) ◽  
pp. 193-196 ◽  
Author(s):  
G Yamashita ◽  
S Tazuma ◽  
G Kajiyama
Keyword(s):  
Bile Salt ◽  
Organic Anion ◽  
Sodium Taurocholate ◽  
Organic Anions ◽  
Phenol Red ◽  
Dependent Manner ◽  
Biliary Lipid ◽  
Lipid Secretion ◽  
Biliary Lipids ◽  
Salt Secretion

This study was performed to determine the effects of various organic anions on biliary lipid secretion in rats. We infused bile-salt-pool-depleted rats with sodium taurocholate at a constant rate, with or without various organic anions: Indocyanine Green (ICG), bromosulphophthalein (BSP), BSP-glutathione and Phenol Red (PR). BSP decreased biliary secretion of cholesterol and phospholipids in a dose-dependent manner without affecting bile salt secretion (uncoupling), and this change was fully reversible. In contrast, ICG, BSP-glutathione and PR did not cause such an uncoupling of biliary lipids. In addition, the distribution pattern of each organic anion to various lipid particles was determined by gel-permeation chromatography. BSP was predominantly associated with bile salt micelles, whereas vesicular association was dominant for ICG, and both BSP-glutathione and PR formed only self-aggregations. From these data, we concluded that the uncoupling of biliary lipids from bile salt secretion by BSP resulted from the interaction between BSP and bile salt micelles in the bile canaliculus, and that this interaction inhibited the capacity of bile salts to induce the secretion of phospholipids and cholesterol.

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 Interactions between organic anions, micelles and vesicles in model bile systems

1996 ◽  
Vol 320 (3) ◽  
pp. 917-923 ◽  
Author(s):  
Henkjan J. VERKADE ◽  
Marjan A. C. de BRUIJN ◽  
Menno A. BRINK ◽  
Herre TALSMA ◽  
Roel J. VONK ◽  
...  
Keyword(s):  
Bile Salt ◽  
Mixed Micelles ◽  
Membrane Lipids ◽  
Organic Anion ◽  
Organic Anions ◽  
In Vitro Models ◽  
Biliary Lipid ◽  
Lipid Secretion

Biliary lipid secretion probably involves both ‘micellization’ and ‘vesiculization’ of bile-canalicular membrane lipids. Several hydrophilic organic anions inhibit the secretion of lipids into the bile without altering bile salt secretion [Verkade, Vonk and Kuipers (1995) Hepatology 21, 1174–1189]. Hydrophobic organic anions do not interfere with biliary lipid secretion. We investigated whether the organic-anion-induced inhibition of biliary lipid secretion in vivo could be attributed to inhibition of micellization, by the application of in vitro models of micellization. Carboxyfluorescein was entrapped in a self-quenching concentration in small unilamellar vesicles (SUV) composed of cholesterol/egg phosphatidylcholine (molar ratios 0, 0.2 and 0.5). Certain organic anions clearly affected the bile-salt-induced release of fluorescence from these SUV, reflecting interference with micellization. However, the effects of hydrophilic and hydrophobic organic anions did not correspond with their effects on biliary lipid secretion in vivo, irrespective of the bile salt species used (taurocholate, taurodeoxycholate or tauroursodeoxycholate) and of the lipid composition of the SUV. Ultracentrifugation and dynamic light-scattering studies indicated that organic anions do interact with bile salt/phosphatidylcholine/cholesterol mixed micelles, but that they do not inhibit micellization, for example by competing with phosphatidylcholine and/or cholesterol for incorporation into mixed micelles. In conclusion, the present in vitro data indicate that the in vivo mechanism of organic-anion-induced inhibition of biliary lipid secretion is not mediated by inhibition of micellization.

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 Control of biliary phospholipid secretion. Effect of continuous and discontinuous infusion of taurocholate on biliary phospholipid secretion

1986 ◽  
Vol 234 (2) ◽  
pp. 421-427 ◽  
Author(s):  
K Rahman ◽  
T G Hammond ◽  
P J Lowe ◽  
S G Barnwell ◽  
B Clark ◽  
...  
Keyword(s):  
Animal Model ◽  
Bile Salt ◽  
Biliary Fistula ◽  
Perfused Liver ◽  
Biliary Lipid ◽  
Short Pulses ◽  
Lipid Secretion ◽  
Canalicular Membrane ◽  
Infusion Period ◽  
Salt Secretion

A major determinant of biliary lipid secretion is bile-salt secretion. Taurocholate (TC), a micelle-forming bile salt, was infused continuously at different rates in both isolated perfused livers and biliary-fistula rats. In both of these systems, infusion of TC brought about an elevated secretion of phosphatidylcholine for the duration of the TC infusion period. Initial phospholipid/bile-salt ratios in the bile were higher in the whole-animal model than in isolated livers, but at the higher infusion rates both secreted approx. 6 mol of phospholipid for every 100 mol of bile salt. The secretion of phospholipid, which was maintained even at high rates of bile-salt infusion, suggest a continuous and regulated phospholipid supply and secretion mechanism. In contrast, however, multiple short pulses of TC to the perfused liver, which brought about relatively equal biliary bile-salt output pulses, did not bring about equal phospholipid outputs, since the phospholipid peak size declined with each bile-salt pulse. These experiments taken together suggest either that a threshold (intracellular) bile-salt concentration may be required to ‘switch-on’ the phospholipid supply and that it may need to be maintained for continuous biliary phospholipid supply to the canalicular membrane.

Effects of sulfobromophthalein excretion on biliary lipid secretion in humans and dogs

1981 ◽  
Vol 240 (1) ◽  
pp. G85-G89
Author(s):  
E. A. Shafter ◽  
R. M. Preshaw
Keyword(s):  
Bile Salt ◽  
Lipid Composition ◽  
Control Period ◽  
Physical Interaction ◽  
Biliary Lipid ◽  
Lipid Secretion ◽  
Maximal Output ◽  
Biliary Lipid Composition ◽  
Molar Percent ◽  
Salt Secretion

The effect of sulfobromophthalein (BSP) on biliary lipid secretion was investigated in 12 cholecystectomized subjects, using a duodenal marker-perfusion technique. A 1-h basal period was followed by intravenous BSP infusion over 3 h, achieving the maximal excretory rate (Tm). The calculated Tm was not different from the measured maximal output. At BSP Tm, bile salt secretion was unchanged, but phospholipid, cholesterol, and bilirubin secretion were markedly reduced. Biliary lipid composition changed accordingly, higher molar percent bile salts but lower phospholipid and cholesterol. In six cholecystectomized dogs with chronic duodenal fistulas, bile was collected directly from the common duct while bile salt secretion was maintained by intravenous taurocholic acid infusion. After a 2-h control period, sufficient BSP was added to create either maximal (Tm) or submaximal conditions. BSP did not alter bile salt secretion but caused a dose-related decrease in phospholipid and cholesterol secretion. Bilirubin excretion was also reduced, whereas bile flow increased. Thus, BSP is hydrocholeretic but decreases phospholipid, cholesterol, and bilirubin secretion in both humans and dogs. The effect on biliary lipid composition is probably through a physical interaction with biliary micelles.

scholarly journals Selective biliary lipid secretion at low bile-salt-output rates in the isolated perfused rat liver. Effects of phalloidin

1986 ◽  
Vol 237 (1) ◽  
pp. 301-304 ◽  
Author(s):  
K Rahman ◽  
R Coleman
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Biliary Lipid ◽  
Perfusion Fluid ◽  
Lipid Secretion ◽  
Rat Livers ◽  
Secretion Rates ◽  
Salt Secretion

At high bile-salt-secretion rates the biliary secretion of phospholipids and cholesterol is dependent on that of the bile salts. However, at low bile-salt outputs some secretion remains. Isolated perfused rat livers were used in these experiments in order to study the bile-salt-independent secretion of biliary lipids. The livers were isolated and saline (0.9% NaCl), or phalloidin dissolved in saline, was added to the perfusion fluid after 1 h of liver isolation. The concentration and output of cholesterol was significantly decreased in phalloidin-treated livers compared with the controls, whereas there was no significant decrease in phospholipids; the secretion of cholesterol and phospholipids can thus be uncoupled from each other by the action of phalloidin. These experiments suggest that a proportion of cholesterol gets into bile independently of bile salts and phospholipids. These findings are discussed in relation to the supersaturation of some biles with cholesterol and its relationship to the bile-salt-independent fraction of cholesterol.

Transient expression of oatp organic anion transporter in mammalian cells: identification of candidate substrates

1996 ◽  
Vol 270 (2) ◽  
pp. F319-F325 ◽  
Author(s):  
N. Kanai ◽  
R. Lu ◽  
Y. Bao ◽  
A. W. Wolkoff ◽  
V. L. Schuster
Keyword(s):  
Hela Cell ◽  
Transient Expression ◽  
Mammalian Cells ◽  
Xenopus Oocytes ◽  
Organic Anion ◽  
Expression System ◽  
Indigo Carmine ◽  
Organic Anions ◽  
Phenol Red ◽  
Cell Monolayers

The cDNA for the rat liver organic anion-transporting polypeptide "oatp" has been shown to encode transport of bromosulfophthalein (BSP) and bile salts in Xenopus oocytes (E. Jacquemin, B. Hagenbuch, B. Stieger, A. W. Wolkoff, and P. J. Meier. Proc. Natl. Acad. Sci. USA 91: 133-137, 1994). Because oatp mRNA is expressed strongly in the kidney, we sought to determine whether renal oatp might play a role in the known secretion of a large variety of organic anions by the kidney. We transiently expressed a full-length oatp cDNA, cloned in pSPORT, in HeLa cell monolayers using the recombinant vaccinia virus vtf7-3. We tested an array of organic anions as candidate substrates by determining their ability to compete with tracer BSP for transport. HeLa cell monolayers transfected with the oatp cDNA transported tracer BSP and taurocholate at rates substantially higher than monolayers transfected with a control plasmid. Thus good expression can be obtained with the vaccinia-HeLa system using a standard plasmid cloning vector. BSP transport varied as a function of the medium albumin, ionic conditions, and pH in a fashion similar to that in Xenopus oocytes. Several organic anions known to be secreted by the classic secretory pathway, including p-aminohippurate (PAH), phenol red, and indigo carmine (10 microM) failed to inhibit oatp-mediated BSP transport. Direct testing using tracers revealed no oatp-mediated transport of sulfate, urate, PAH, several eicosanoids, or unconjugated or conjugated bilirubin. On the other hand, BSP transport was inhibited by approximately 50% by 10 microM corticosterone sulfate, spironolactone, and several other steroids. We conclude that the functional properties of oatp expressed in the HeLa cell/vaccinia transient expression system are comparable to those following expression in Xenopus oocytes and that steroids are likely to represent high-affinity endogenous oatp substrates. The latter hypothesis is addressed in greater detail in a companion paper.

scholarly journals The importance of membrane microdomains for bile salt-dependent biliary lipid secretion

2018 ◽  
Vol 131 (5) ◽  
pp. jcs211524 ◽  
Author(s):  
Johannes Eckstein ◽  
Hermann-Georg Holzhütter ◽  
Nikolaus Berndt
Keyword(s):  
Bile Salt ◽  
Membrane Microdomains ◽  
Biliary Lipid ◽  
Lipid Secretion
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