Effect of albumin on bile acid uptake by isolated rat hepatocytes is there a common bile acid carrier?

Anwer, Muhammad; Kroker, R.; Hegner, D.

doi:10.1016/0006-291x(76)90497-6

Cited by 52 publications

(10 citation statements)

References 5 publications

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“…Furthermore, it is not clear whether the transport system for hepatic uptake is common to all bile acids species (34). Carrier-mediated transport systems have also been proposed at the canalicular pole of the hepatocyte (9,10,33).…”

Section: Resultsmentioning

confidence: 99%

Separate transport systems for biliary secretion of sulfated and unsulfated bile acids in the rat.

Kuipers

Enserink²,

Havinga³

et al. 1988

J. Clin. Invest.

129

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Biliary secretion of 3a-sulfated bile acids has been studied in Wistar rats with an autosomal recessive defect in the hepatic transport of bilirubin. Liver function, established by measurement of various enzymes in plasma, by enzyme histochemical methods, and by electron microscopy, appeared to be normal in these rats. Serum levels of unconjugated, monoglucuronidated, and diglucuronidated bilirubin were 0.62, 1.62, and 6.16 Mmol/ liter, respectively, compared with 0.17, 0.08, and 0.02 gmol/ liter in control rats. Biliary bilirubin secretion was strongly reduced in the mutant animals: 0.21±0.03 vs. 0.39±0.03 nmol/min per 100 g body wt in control rats. Despite normal biliary bile acid output, bile flow was markedly impaired in the mutant animals, due to a 53% reduction of the bile acid-independent fraction of bile flow. The transport maximum for biliary secretion of dibromosulphthalein (DBSP) was also drastically reduced (-53%).Biliary secretion of intravenously administered trace amounts of the 3a-sulfate esters of '4C-labeled taurocholic acid (-14%), taurochenodeoxycholic acid (-39%), taurolithocholic acid (-73%), and glycolithocholic acid (-91%) was impaired in the jaundiced rats compared with controls, in contrast to the biliary secretion of the unsulfated parent compounds. Hepatic uptake of sulfated glycolithocholic acid was not affected in the jaundiced animals. Preadministration of DBSP (15 gmol/100 g body wt) to normal Wistar rats significantly impaired the biliary secretion of sulfated glycolithocholic acid, but did not affect taurocholic acid secretion.We conclude that separate transport systems in the rat liver exist for biliary secretion of sulfated and unsulfated bile acids; the sulfates probably share secretory pathways with the organic anions bilirubin and DBSP. The described genetic defect in hepatic transport function is associated with a reduced capacity to secrete sulfated bile acids into bile; this becomes more pronounced with a decreasing number of hydroxyl groups on the sulfated bile acid's molecule.

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Section: Resultsmentioning

confidence: 99%

Separate transport systems for biliary secretion of sulfated and unsulfated bile acids in the rat.

Kuipers

Enserink²,

Havinga³

et al. 1988

J. Clin. Invest.

129

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“…In this situation it was worthful to find compounds with divergent effects of the uptake of conjugated versus unconjugated bile acids. In an early study albumin inhibited CA uptake noncompetitively but TCA uptake competitively (Anwer et al 1976b). This suggests that bile acids are not transported by a common carrier.…”

Section: How Many Bile Acid Carriers Exist? Biochemical Studies On Thmentioning

confidence: 99%

Transport of organic anions in the liver. An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport

Petzinger¹

1994

Reviews of Physiology, Biochemistry and Pharmacology

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“…Thus, it is assumed that virtually instantaneous equilibration occurs between bound and unbound ligand. The conventional theory was first challenged by Baker and Bradley (10), who concluded that hepatic sulfobro- (12). Although provocative, these issues went almost unnoticed for ten years until more recent observations confirmed and expanded the controversy.…”

Section: Introductionmentioning

confidence: 99%

“…(1 1), and Anwer et al (12). The precise mechanism for the surface-mediated dissociation of ligand/albumin complexes proposed by Forker and associates ( 14) was not defined, but a variety ofalternative explanations for the kinetic observations, including nonequilibrium binding of ligand to albumin and the effects of an unstirred water layer in Disse's space were considered but rejected on the basis of detailed mathematical analysis (33).…”

Section: Introductionmentioning

confidence: 99%

At physiologic albumin/oleate concentrations oleate uptake by isolated hepatocytes, cardiac myocytes, and adipocytes is a saturable function of the unbound oleate concentration. Uptake kinetics are consistent with the conventional theory.

Sorrentino¹,

Robinson²,

Kiang³

et al. 1989

J. Clin. Invest.

128

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To reexamine the role of albumin in cellular uptake of long chain fatty acids, we measured I3HIoleate uptake by isolated hepatocytes, adipocytes, and cardiac myocytes from incubations containing oleate/albumin complexes at molar ratios from 0.01:1 to 2:1. For each ratio the uptake was studied over a wide range of albumin concentrations. In all three cell types and at any given oleate/albumin ratio, the uptake appeared saturable with increasing concentrations of oleate:albumin complexes despite the fact that the unbound oleate concentration for each molar ratio is essentially constant. However, the "K."' but not the "V,,,,C" of these pseudosaturation curves was influenced by substrate availability. At low albumin concentrations, uptake velocities did not correlate with unbound oleate concentrations. However, observed and expected uptake velocities coincided at albumin concentrations approaching physiologic levels and were a saturable function of the oleate/albumin ratios and the consequent unbound oleate concentrations employed. Hence, under the experimental conditions employed in this study using a variety of suspended cell types, oleate uptake kinetics were consistent with the conventional theory at physiologic concentrations of albumin.

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Effect of albumin on bile acid uptake by isolated rat hepatocytes is there a common bile acid carrier?

Cited by 52 publications

References 5 publications

Separate transport systems for biliary secretion of sulfated and unsulfated bile acids in the rat.

Separate transport systems for biliary secretion of sulfated and unsulfated bile acids in the rat.

Transport of organic anions in the liver. An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport

At physiologic albumin/oleate concentrations oleate uptake by isolated hepatocytes, cardiac myocytes, and adipocytes is a saturable function of the unbound oleate concentration. Uptake kinetics are consistent with the conventional theory.

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