Biliary Lipid Secretion and its Control

Coleman, Roger; Rahman, Khalid; Bellringer, Maria; Carrella, M.

doi:10.1007/978-94-009-1249-6_4

Cited by 8 publications

(5 citation statements)

References 62 publications

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“…The mechanism of lipid excretion from hepatocytes into the bile canalicular lumen is not completely understood. Coleman et al 32 . postulated that phospholipids and cholesterol synthesized in the hepatocytes are transferred intracellulary to vesicles and then excreted into the canalicular lumen, where they combine with bile acids to form mixed micelles.…”

Section: Discussionmentioning

confidence: 99%

“…Coleman et al . 32 postulated that phospholipids and cholesterol synthesized in the hepatocytes are transferred intracellulary to vesicles and then excreted into the canalicular lumen, where they combine with bile acids to form mixed micelles. Bile acids were proposed to preferentially solubilize specific, highly fluid lipid 'microdomains' representing the fusion points of the canalicular membrane with repair vesicles carrying lipids and surface enzymes derived from the interior of the hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

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Choleresis and inhibition of biliary lipid secretion induced by piperacillin in the rat

González

Mauriz

Jiménez

et al. 2002

Clin Exp Pharma Physio

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1. The effects of the administration piperacillin on bile flow and biliary lipid secretion were studied in male Wistar rats. 2. Intravenous injection of piperacillin at doses ranging from 0.3 to 3.0 mmol/kg bodyweight led to an increase in its biliary concentration and excretion rate. Maximal biliary excretion was reached at a dose of 2.0 mmol/kg piperacillin. 3. Excretion of the antibiotic into bile was associated with a marked choleresis. A linear relationship was observed between bile flow and piperacillin excretion, 5.7 micro L bile being produced per micro mol piperacillin excreted into the bile. 4. Continuous i.v. infusion of piperacillin at 2.0 mmol/100 g per min did not result in significant changes in bile acid or cholesterol secretion, but biliary phospholipid secretion was markedly reduced. The inhibitory effect on phospholipid secretion was also present when biliary lipid output had been previously increased by an infusion of taurocholate (200 nmol/100 g per min). Addition of taurocholate did not reverse the impairment of phospholipid secretion induced by piperacillin. 5. These results indicate that acute administration of piperacillin in the rat induces a marked choleresis by stimulating bile acid-independent bile flow. The significant impairment in phospholipid secretion suggests a specific effect on intracellular supply and/or translocation across the canalicular membrane.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Choleresis and inhibition of biliary lipid secretion induced by piperacillin in the rat

González

Mauriz

Jiménez

et al. 2002

Clin Exp Pharma Physio

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“…These observations suggest that a vesicular transport system is involved in cholesterol and phospholipid secretion. Vesicular fractions enriched with biliary type phosphatidylcholine have been isolated in rat liver exposed to taurodehydrocholic acid [70]. Ahmed et al [71,72] have recently isolated a vesicular fraction from human liver homogenates having an enzymic composition similar to that of the microsomes and of the bile canalicular membrane, but different from that of other plasma membrane domains.…”

Section: Biliary Lipid Couplingmentioning

confidence: 99%

Biliary lipid secretion in man

Lanzini

Northfield

1991

Eur J Clin Investigation

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“…4 However, these ratios are maintained during moderate changes in overall secretion rates, as bile acid output rises and falls. 5,6 In certain pathologic conditions where the secretion of cholesterol is excessive, i.e., out of balance with phospholipids and bile salts, the bile becomes supersaturated with cholesterol. This leads to the precipitation of cholesterol crystals in bile and eventually to the formation of cholesterol gallstones.…”

mentioning

confidence: 99%

Regulation of multidrug resistance 2 P-glycoprotein expression by bile salts in rats and in primary cultures of rat hepatocytes

et al. 2000

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Biliary phospholipid secretion is tightly coupled to the secretion of free cholesterol and bile salts. The secretion of phospholipids across the canalicular membrane of hepatocytes occurs via the multidrug resistance 2 (mdr2) P-glycoprotein (Pgp). The mechanism underlying the coupling of bile salt and phospholipid secretion has not been elucidated. The aims of this study were to determine the effects of bile acid structure on the expression of mdr2 in vitro and in vivo. Under optimal culture conditions, taurine-conjugated bile acids (50 mol/L) increased mdr2 messenger RNA (mRNA) levels in the following order: taurocholate (TCA) (288 ؎ 36%, P < .005) ‫؍‬ taurodeoxycholate (TDCA) (276 ؎ 36%, P < .025) > taurochenodeoxycholate (TCDCA) (216 ؎ 34%, P < .025) > tauroursodeoxycholate (TUDCA) (175 ؎ 28%, P < .05) of control levels. The increase in mdr2 mRNA levels by TCA was both time and concentration dependent. Cholate feeding to rats with intact enterohepatic circulation increased mdr2 transcriptional activity by 4-fold and protein mass by 1.9-fold. Chronic biliary diversion (CBD) decreased mdr2 mRNA levels to 66 ؎ 9% (P < .025) of shamoperated controls. Intraduodenal infusion of TCA for 48 hours in CBD rats caused a significant increase in mdr2 mRNA levels (224%) as compared with CBD controls. A diet high in cholesterol (4%) decreased mdr2 mRNA levels to 57% ؎ 2 (P < .001) of pair-fed controls. Squalestatin (1 mol/L), an inhibitor of cholesterol biosynthesis, increased mdr2 mRNA levels by 8.8-fold (P < .005) in hepatocyte cultures after 24 hours. In conclusion, in the rat, bile acids up-regulated mdr2 transcriptional activity whereas cholesterol decreased mdr2 mRNA both in vitro and in vivo. (HEPATOLOGY 2000;32:341-347.)The coupling of biliary secretion of bile salts, phosphatidylcholine (PC) and cholesterol is important in the maintenance of bile flow, biliary lipid composition, and the solubilization of cholesterol. The secretion of PC into the bile is tightly linked to that of cholesterol and the flux of both lipids are coordinated with that of bile salts. 1-3 The biliary cholesterol: phospholipid ratios vary substantially in different species (human 0.3, rat 0.1). 4 However, these ratios are maintained during moderate changes in overall secretion rates, as bile acid output rises and falls. 5,6 In certain pathologic conditions where the secretion of cholesterol is excessive, i.e., out of balance with phospholipids and bile salts, the bile becomes supersaturated with cholesterol. This leads to the precipitation of cholesterol crystals in bile and eventually to the formation of cholesterol gallstones. 4,7 Several studies have described a hyperbolic relationship between rates of bile salt, phospholipid, and cholesterol secretion. 3,8 As bile salt output increases, the rate of biliary lipid secretion also increases until a maximum is reached. 9,10 Moreover, the rate of lipid secretion is proportional to the hydrophobicity of the secreted bile salt species. 7,11 Because hydrophobic bile salts have a greater detergent ...

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Biliary Lipid Secretion and its Control

Cited by 8 publications

References 62 publications

Choleresis and inhibition of biliary lipid secretion induced by piperacillin in the rat

Choleresis and inhibition of biliary lipid secretion induced by piperacillin in the rat

Biliary lipid secretion in man

Regulation of multidrug resistance 2 P-glycoprotein expression by bile salts in rats and in primary cultures of rat hepatocytes

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