Mechanism of secretion of biliary lipids. I. Role of bile canalicular and microsomal membranes in the synthesis and transport of biliary lecithin and cholesterol.

Gregory, Daniel H.; Vlahčevič, Z. Reno; Schatzki, Peter F.; Swell, Leon

doi:10.1172/jci107900

Cited by 80 publications

(27 citation statements)

References 33 publications

(32 reference statements)

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“…This is in agreement with recent reports from different laboratories (32,(39)(40)(41)(42). This bile LP revealed a lipid composition almost identical to LP-X but differed from LP-X in protein/lipid ratio and immunological and electrophoretic characteristics.…”

Section: Resultssupporting

confidence: 93%

Formation of lipoprotein-X. Its relationship to bile compounds.

Manzato¹,

Fellin²,

Baggio³

et al. 1976

J. Clin. Invest.

139

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A B S T R A C T In this study we have demonstrated that in native bile, lipids are organized in the form of a lipoprotein (bile LP) carrying albumin as apoprotein. The lipid composition of bile LP is almost identical to lipoprotein-X (LP-X, the characteristic lipoprotein of cholestasis). However, it differs from LP-X in its protein/lipid ratio and immunological and electrophoretic characteristics. Bile lipoprotein can be converted into "LP-X-like" material in vitro by adding albumin or serum to native bile. The LP-X-like material formed in vitro has physicochemical and chemical characteristics similar or identical to LP-X isolated from serum. As bile lipoprotein can be converted into LP-X-like material by the addition of albumin to bile, LP-X can be converted into bile-LP-like particles by adding bile salts to a LP-X-positive serum. Furthermore, experimental connection of the common bile duct to the vena cava is followed after a few hours by the appearance of LP-Xlike material in the plasma. These facts taken together strongly suggest that bile LP is a precursor lipoprotein for LP-X and that it refluxes into the plasma pool under cholestatic conditions.

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Section: Resultssupporting

confidence: 93%

Formation of lipoprotein-X. Its relationship to bile compounds.

Manzato¹,

Fellin²,

Baggio³

et al. 1976

J. Clin. Invest.

139

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“…To account for this selection process, it was postulated that there was a small pool of hepatic PC that was specifically destined for biliary secretion. [9][10][11] Others postulated that the more hydrophilic PC species were selected for secretion, 12 possibly as a consequence of physical-chemical interactions of bile salts with hepatic membranes. [13][14][15] However, while bile salts clearly influence the overall rate of phospholipid secretion, differences in hydrophobicity provide a very incomplete explanation for selection of particular PC species.…”

Section: Discussionmentioning

confidence: 99%

“…4,[7][8][9] The distinctive composition of biliary PC was initially attributed to its origination from a small pool in the liver that was specifically destined for biliary secretion. [9][10][11] It was further postulated that the more hydrophilic PC species were selected for secretion, 12 possibly as a consequence of physical-chemical interactions of bile salts with hepatic membranes. [13][14][15] However, other observations indicate that differences in hydrophobicity provide, at best, an incomplete explanation for PC selection, 6,17,18 and that other factors, such as differences in acyl chain length, may correlate with selection.…”

mentioning

confidence: 99%

Determinants of the selection of phosphatidylcholine molecular species for secretion into bile in the rat

1998

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Certain phosphatidylcholine (PC) molecular species appear to be secreted into bile preferentially, but the mechanism for this selection remains obscure. We used multivariate analysis to examine the relationship between PC structure and the odds of secretion for individual PC species secreted into bile. PC was isolated from Folch extracts of bile and liver from rats, and individual molecular species of PC were quantified with reverse-phase highperformance liquid chromatography (HPLC). The odds of secretion for a given PC species were quantified as the ratio of its mole % in bile/mole % in liver. Regression analysis indicated that the odds of secretion were significantly related to length of both the sn-1 and sn-2 acyl chains (P F .0001 for both) and to relative hydrophobicity as determined by reverse-phase HPLC (P F .0001). In addition, the relationship between odds of secretion and sn-1 chain length was best described by a parabolic function. Considered together, these characteristics accounted for 88% of the observed differences in odds of secretion. This relationship between PC structure and odds of secretion was strikingly similar to the relationship between PC structure and affinity for bovine PC transfer protein. When multivariate models were used to predict both the odds of secretion and the affinity for PC transfer protein for a set of biologically plausible PC species, there was a linear relationship between the two. The likelihood of a given PC species being secreted into bile can be related to the structural characteristics of the acyl chains without having to postulate the existence of a special pool of PC destined for biliary secretion. Second, the structural characteristics that dictate selection of PC species for secretion into bile are similar to those that determine binding affinity for PC transfer protein, suggesting that the likelihood of a PC being secreted into bile is, in fact, closely related to its binding affinity for PC transfer protein (PC-TP). (HEPATOLOGY 1998;28:631-637.)There is abundant evidence that the biliary secretion of bile salts, phospholipids, and cholesterol are intimately linked, [1][2][3]

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“…Subsequent infusions ofbile acids might then have less ofa modifying effect, but the question remains to be explained. Nevertheless, the observation is clear and appears to be related specifically to the structure of bile acids as this phenomenon was seen only with the infusion of taurocholate, a micelle-forming bile acid which also stimulates hepatic phospholipid synthesis and excretion (24,25), but was not observed with infusions of dehydrocholate, a bile acid which does not alter phospholipid metabolism (14). Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Scanning electron microscopic studies from our laboratory demonstrated irregularities and outpouchings in the canalicular surface membranes Bile Flow (ml/24h) 300 FIGURE 8 Predicted differences in the diffusion permeability constant (K) during administration of7.0 ,umol/min taurocholic acid followed by 3.5 ,umol/min (solid lines) and 3.5 umol/min taurocholic acid followed by 7 of rats infused with bile acids, alterations which might occur through such a bile acid-canalicular membrane interaction and account for some of the differences in choleretic effect which we observed. In addition, an initial infusion of 7.0 gmol/min taurocholic acid might produce an increase in hepatic synthesis of phosphatydyl choline (24,25), thus resulting in an increase in the phospholipid:cholesterol ratio in canalicular membranes and enhanced membrane permeability, an effect not observed with dehydrocholic acid (14). Alteration in the permeability of the hepatocyte junctional complexes is yet another mechanism whereby taurocholate may increase the biliary clearance of inulin and augment its choleretic effect, particularly because recent studies in the rat indicate that taurocholate and taurodehydrocholate-induced choleresis increase hepatocyte junctional permeability to ionic lanthanum (16).…”

Section: Discussionmentioning

confidence: 99%

Sodium Taurocholate Modifies the Bile Acid-Independent Fraction of Canalicular Bile Flow in the Rhesus Monkey

Baker¹,

Wood²,

Moossa³

et al. 1979

J. Clin. Invest.

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A B S T R A C T Bile acid-independent secretion and the choleretic response to taurocholate were determined in rhesus monkeys fitted with indwelling silastic cannulas in the common bile ducts. Bile acids were infused intravenously in random order at 3.5, 7.0, or 10.5 ,umol/min for 1.5 h each. When data were analyzed with a single regression line, bile flow increased in proportion to the level of bile acid secretion, although the y-intercepts (the conventional measurement ofbile acid-independent secretion) varied widely (77.9±40.9 ml/24 h). The variation in y-intercepts was observed between animals and with repeated studies in the same animal and could not be explained by sex differences or the effects of the indwelling silastic cannulas, but seemed to be related to the order of bile acid infusion. With only two taurocholic acid infusion rates (7.0 and 3.5 ,umol/min), [Q4C]erythritol clearance was greater per mole of secreted bile acid when the initial bile acid infusion was at the high level, but approached zero at low bile acid secretion rates, which suggests that socalled bile acid-independent canalicular flow is closely related to bile acid secretion or is small in size. The augmentation in [14C]erythritol clearance when the high infusion rate was given first was also associated with an increase in biliary clearance of [3H]

show abstract

Mechanism of secretion of biliary lipids. I. Role of bile canalicular and microsomal membranes in the synthesis and transport of biliary lecithin and cholesterol.

Cited by 80 publications

References 33 publications

Formation of lipoprotein-X. Its relationship to bile compounds.

Formation of lipoprotein-X. Its relationship to bile compounds.

Determinants of the selection of phosphatidylcholine molecular species for secretion into bile in the rat

Sodium Taurocholate Modifies the Bile Acid-Independent Fraction of Canalicular Bile Flow in the Rhesus Monkey

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