Biochemical and molecular aspects of the hepatic uptake of organic anions

Tiribelli, Claudio; Lunazzi, Gian Carlo; Sottocasa, Gian Luigi

doi:10.1016/0304-4157(90)90012-2

Cited by 71 publications

(50 citation statements)

References 111 publications

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“…We selected three organic anions (PR, BPB and BSP) as a model drug because their disposition characteristics in liver had been investigated (Klaassen & Watkins III 1984;Tiribelli et al 1986Tiribelli et al , 1990Hart & Schanker 1966;Moller & Sheikh 1983;Kakutani et al 1992). Fig.…”

Section: Resultsmentioning

confidence: 99%

Absorption of Organic Anions as Model Drugs Following Application to Rat Liver Surface In-vivo

Nishida

Satô

Sasaki

et al. 1994

Journal of Pharmacy and Pharmacology

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Absorption of organic anions (phenol red, bromphenol blue and bromosulphonphthalein) has been studied after their application to rat liver surface in-vivo, employing a cylindrical glass cell (i.d. 9 mm, area 0.64 cm2).Every drug appeared gradually in the blood with the peak level at about 1 h, after which its concentration declined slowly. Absorbed model drug was efficiently excreted into the bile. These observations appear to indicate the possibility of drug absorption from liver surface membrane. Absorption ratios of model drugs were estimated to be more than 59 % in 6 h. As to phenol red, its biliary recovery and metabolism ratio did not change as compared with that of i.v. administration.

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Section: Resultsmentioning

confidence: 99%

Absorption of Organic Anions as Model Drugs Following Application to Rat Liver Surface In-vivo

Nishida

Satô

Sasaki

et al. 1994

Journal of Pharmacy and Pharmacology

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“…These buffers were chosen to allow comparison with earlier vesicle transport studies using the same preparations of [ 14 C]bilirubin and albumin (47,48) and not to simulate neonatal plasma. Thus, neither our values of K F , nor those obtained by other methods (3) may represent the true affinity of bilirubin for HSA in the plasma of jaundiced neonates, and further studies are needed to determine the K F values in neonatal plasma.…”

Section: Table I Estimates Of Impurity Levels and Formation Rates Usimentioning

confidence: 99%

Affinity of Human Serum Albumin for Bilirubin Varies with Albumin Concentration and Buffer Composition

Weisiger¹,

Ostrow²,

Koehler³

et al. 2001

Journal of Biological Chemistry

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107

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Albumin binding is a crucial determinant of bilirubin clearance in health and bilirubin toxicity in certain disease states. However, prior attempts to measure the affinity of albumin for bilirubin have yielded highly variable results, reflecting both differing conditions and the confounding influence of impurities. We therefore have devised a method based on serial ultrafiltration that successively removes impurities in [ 14 C]bilirubin until a stable binding affinity is achieved, and then we used it to assess the effect of albumin concentration and buffer composition on binding. The apparent binding affinity of human serum albumin for [ 14 C]bilirubin was strongly dependent on assay conditions, falling from (5.09 ؎ 0.24) ؋ 10 7 liters/mol at lower albumin concentrations (15 M) to (0.54 ؎ 0.05) ؋ 10 7 liters/mol at higher albumin concentrations (300 M). To determine whether radioactive impurities were responsible for this change, we estimated impurities in the stock bilirubin using a novel modeling approach and found them to be 0.11-0.13%. Formation of new impurities during the study and their affinity for albumin were also estimated. After correction for impurities, the binding affinity remained heavily dependent on the albumin concentration (range (5.37 ؎ 0.26) ؋ 10 7 liters/mol to (0.65 ؎ 0.03) ؋ 10 7 liters/ mol). Affinities decreased by about half in the presence of chloride (50 mM). Thus, the affinity of human albumin for bilirubin is not constant, but varies with both albumin concentration and buffer composition. Binding may be considerably less avid at physiological albumin concentrations than previously believed.

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“…98 Studies without albumin will proteins involved in the hepatocytic transport of bilirubin also overlook the role of albumin in facilitating diffusion of and other cholephilic organic anions, such as BSP and fatty hydrophobic ligands across the unstirred water layer 51,99 and acids. 7,80,81 the regulatory effects of competitors for albumin binding of In the classical approach, the binding protein(s) in the the ligand. 56 Assessment of the relative roles of transport membrane are identified either by photoaffinity labeling with proteins by inhibition of their function with antibodies 100 may a modified substrate [82][83][84] or by selective adsorption to highbe confounded by several factors: (1) significant passive affinity ligands covalently linked to support columns.…”

Section: Hepatocytic Transport Proteinsmentioning

confidence: 99%

New Concepts in Bilirubin and Jaundice: Report of the Third International Bilirubin Workshop, April 6–8, 1995, Trieste, Italy

Tiribelli

Ostrow

1996

Hepatology

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only partial and temporary relief of hyperbilirubinemia; tocytic transporters of UCB and related organic anions extracorporeal liver assist devices have had some sucwere described. Special emphasis was given to the adencess in initial human studies; and inhibition of heme osine triphosphate (ATP)-dependent canalicular multioxygenase (HO) with metalloporphyrins, especially tin specific organic anion transporter that is defective in mesoporphyrin, which markedly decreases bilirubin production for prolonged periods, is a new alternative dipyrrole (Fig. 1). In solution, however, this structure is flexi- Received October 3, 1995; accepted June 6, 1996. ble, and small changes ({40Њ) in the interplanar angle (u)

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Biochemical and molecular aspects of the hepatic uptake of organic anions

Cited by 71 publications

References 111 publications

Absorption of Organic Anions as Model Drugs Following Application to Rat Liver Surface In-vivo

Absorption of Organic Anions as Model Drugs Following Application to Rat Liver Surface In-vivo

Affinity of Human Serum Albumin for Bilirubin Varies with Albumin Concentration and Buffer Composition

New Concepts in Bilirubin and Jaundice: Report of the Third International Bilirubin Workshop, April 6–8, 1995, Trieste, Italy

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