Regulation of hepatic transport of bile salt. Effect of protein synthesis inhibition on excretion of bile salts and their binding to liver surface membrane fractions.

Gonzalez, Manuel; Sutherland, Earl W.; Simon, Francis R.

doi:10.1172/jci109351

Cited by 37 publications

(15 citation statements)

References 55 publications

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“…Ethinyl estradiol treatment significantly reduced Na+-K+-ATPase activity (54%), BSIBF (67%), and bile salt Tm (56%), whereas Triton WR-1339 returned these parameters to control levels (Table V). Cycloheximide administration did not prevent Triton WR-1339 reversal of either Na+-K+-ATPase activity or BSIBF in the ethinyl estradiol-treated rat, although the dose employed (150 ug/100 g body wt) has previously been shown to inhibit protein synthesis and decrease bile acid Tm, as well as prevent phenobarbital induction of Na+-K+-ATPase and bile flow (16,25).…”

Section: Resultsmentioning

confidence: 84%

“…Since in vitro binding kinetic characteristics are similar to those for bile acid transport (7,13) and since a parallel decrease in transport and the number of bile acid binding sites are observed after cycloheximide administration, it has been proposed that the bile acid receptor represents the putative bile acid carrier (13,25 administered phenobarbital, a drug also known to increase Na+-K+-ATPase activity (8,16) to examine whether restoration of normal transport function may be possibly related to changes in sodium pump activity. Phenobarbital administered simultaneously with ethinyl estradiol restored basal bile flow, BSIBF, and Na+-K+-ATPase activity to values not significantly different from control (Table III).…”

Section: Resultsmentioning

confidence: 99%

“…This conclusion is strengthened by the findings that similar enzyme activity alterations are observed in the homogenate. Furthermore (25).…”

Section: Discussionmentioning

confidence: 99%

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Reversal of Ethinyl Estradiol-induced Bile Secretory Failure with Triton WR-1339

Simon¹,

Gonzalez²,

Sutherland³

et al. 1980

J. Clin. Invest.

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Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Reversal of Ethinyl Estradiol-induced Bile Secretory Failure with Triton WR-1339

Simon¹,

Gonzalez²,

Sutherland³

et al. 1980

J. Clin. Invest.

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“…Maximal transport capacity for bile salts and BSP was measured as previously described (14). To determine bile salt Tm, taurocholate was infused through either the subclavian or the femoral vein using a PE 50 catheter.…”

Section: Methodsmentioning

confidence: 99%

“…Several lines of evidence have suggested that bile salt carriers are important in the regulation of bile secretion: (a) bile salt receptors, whose affinity is independent of the sodium concentration, have been identified and characterized in liver surface membrane fractions (13); and (b) maximum taurocholate excretion rates decrease as the number of bile salt receptors decreases (14). In addition to the number of bile salt carriers, membrane lipid composition and fluidity are also major determinants of bile salt excretion (15,16).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Bile Salt Transport in Rat Liver

Simon¹,

Sutherland²,

Gonzalez³

1982

J. Clin. Invest.

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A B S T R A C T Expansion of the bile salt pool size in rats increases maximum excretory capacity for taurocholate. We examined whether increased bile salt transport is due to recruitment of centrolobular transport units or rather to adaptive changes in the hepatocyte. Daily sodium cholate (100 mg/100 g body wt) was administered orally to rats. This treatment was well tolerated for at least 4 d and produced an 8.2-fold expansion of the bile salt pool. This expanded pool consisted predominently (99%) of cholic and deoxycholic acids. Significantly increased bile salt transport was not observed until 16 h after bile acid loading, and maximum elevations of transport capacity to 2.3-fold of control required -2 d. In contrast, maximum sulfobromophthalein excretion rates increased 2.2-fold as early as 4 h and actually fell to 1.5-fold increase at 4 d. We studied the possibility that this adaptive increase in bile salt secretory transport was due to changes in canalicular surface membrane area, lipid composition, or increased number of putative carriers. Canalicular membrane protein recovery and the specific activities of leucine aminopeptidase, Mg++-ATPase and 5'-nucleotidase activities were unaltered by bile salt pool expansion. The content of free and esterified cholesterol and total phospholipids was unchanged in liver surface membrane fractions compared with control values. In contrast, sodium cholate administration seThis work was presented, in part,

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Membrane traffic at the hepatocyte’s sinusoidal and canalicular surface domains

Evans¹

1981

Hepatology

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Traffic in the environs of regions of the hepatocyte's plasma membrane is heavy. A fuller understanding of the nature and control of this membrane traffic depends on the appreciation of the hepatocyte's plasma membrane. This conglomerate consists of a receptor-rich and metabolically dynamic blood-sinusoidal domain which is separated from the bile canalicular domain by a lateral domain which participates in cell-cell interactions (1, 2). The rapid receptor-mediated endocytotic uptake and processing of membrane receptor-ligand complexes occurring against a background of hepatic secretion is a key step in understanding relationships between intracellular membrane compartments and the maintenance of differentiated plasma membrane domains. The fate of a wide range of interiorized ligands appears to be decided upon transfer to a Golgi-endoplasmic reticulum lysosomal (GERL) locus where a processing decision is made leading to release of ligands in an intact form into sinusoids or bile canaliculi, or to degradation. This review discusses properties of receptor-binding sites for hormones and metabolites which are located primarily at the sinusoidal plasma membrane, the biogenesis of this membrane, and the various traffic routes of membrane-ligand complexes traversing the hepatocyte interior.THE HEPATOCYTE'S RECEPTOR-RICH SINUSOIDAL PLASMA MEMBRANE DOMAIN A large number of specific-binding sites for hormones and metabolites are at the sinusoidal aspect of the hepatocyte's surface. So extensive has the list of receptorbinding moieties become ( Table 1) that probably few molecules cross the plasma membrane barrier without the appropriate translocating signals which are recognized by membrane receptors. Receptor-mediated binding and subsequent uptake of membrane ligand complexes have achieved increasing importance as compared to absorptive-passive transfer into the hepatocyte. The paracellular shunt pathway into bile is confined mainly to small ions and water (3). Most of the binding sites in Table 1 are accounted for by discrete receptors which invite isolation and molecular characterization. Some hormones, e.g., prolactin and somatotropin, probably bind to the same receptor (4, 5). Studies of the action on liver metabolism of parathyroid hormone suggest a role for nonparenchymal liver cells; processing by peptide cleavage may be required for presentation of the correct polypeptide hormone fragment to the hepatocyte surface receptor (6). Intercellular metabolic cooperation between hepatocytes and surrounding cells has also been suggested in the uptake of carcinoembryonic antigen (7).Because steroid hormones are lipophilic compounds which could be taken up by diffusion, it may appear surprising that hepatocyte plasma membrane steroid receptor sites have been identified in addition to those in cytosol and nucleus (8). These high-affinity estrogenbinding sites are clearly distinguished from sites in estrogen degradation and modification. Plasma membrane steroid receptors are probably widely distributed on target tissues; e.g., ...

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Regulation of hepatic transport of bile salt. Effect of protein synthesis inhibition on excretion of bile salts and their binding to liver surface membrane fractions.

Cited by 37 publications

References 55 publications

Reversal of Ethinyl Estradiol-induced Bile Secretory Failure with Triton WR-1339

Reversal of Ethinyl Estradiol-induced Bile Secretory Failure with Triton WR-1339

Regulation of Bile Salt Transport in Rat Liver

Membrane traffic at the hepatocyte’s sinusoidal and canalicular surface domains

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