Effects of ion substitution on bile acid-dependent and -independent bile formation by rat liver.

Dyke, Rebecca W. Van; Stephens, J. E.; Scharschmidt, Bruce F.

doi:10.1172/jci110642

Cited by 64 publications

(34 citation statements)

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“…Experimental systems Isolated perfused rat liver. The surgical techniques, design, and operation of the perfused rat liver apparatus used in these studies have been described in detail previously (17)(18)(19). A constant perfusion rate of 25 ml/min was maintained in all studies and net portal perfusion pressure was <5 cm H20 during all experiments.…”

Section: Analytical and Preparative Techniquesmentioning

confidence: 99%

“…This system using perfusate containing 20% (vol/vol) fluorocarbon emulsion (Fluosol-43) as an oxygen carrier has been extensively validated. Viability of the perfused liver for perfusions up to 3 h has been shown by normal appearance by electron microscopy, stable perfusate lactate dehydrogenase and transaminase activity, and normal hepatic oxygen consumption (17)(18)(19).…”

Section: Analytical and Preparative Techniquesmentioning

confidence: 99%

“…The first 30 min represented a stabilization period in which the liver was perfused with bile acid-free and marker-free fluorocarbon-containing perfusate. At 30 min, a new perfusate containing appropriate marker(s) was abruptly introduced into the system as previously described (17)(18)(19) so as to produce a "square-wave" increase in marker concentration.…”

Section: Analytical and Preparative Techniquesmentioning

confidence: 99%

“…At 75 min, marker was flushed from the system by a 2-min period of nonrecirculating perfusion with marker-free Krebs-Hensleit buffer followed by 43 min of recirculating perfusion with marker-free perfusate in a fashion similar to that previously employed for ion substitution experiments (17)(18)(19). Finally, to assess the possible effect of bile acids on washout of residual liver-associated marker, a 2.5-Mmol bolus of taurocholate was introduced at 120 min followed by taurocholate infusion for the final 30 min (18).…”

Section: Analytical and Preparative Techniquesmentioning

confidence: 99%

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Biliary secretion of fluid-phase markers by the isolated perfused rat liver. Role of transcellular vesicular transport.

et al. 1985

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In these studies, we have used several approaches to systematically explore the contribution of transcellular vesicular transport (transcytosis) to the blood-to-bile movement of inert fluid-phase markers of widely varying molecular weight. First, under steady-state conditions, the perfused rat liver secreted even large markers in appreciable amounts. The bile-to-plasma (B/P) ratio of these different markers, including microperoxidase (B/P ratio = 0.06; mol wt = 1,879), inulin (B/P ratio = 0.09, mol wt = 5,000), horseradish peroxidase (B/P ratio = 0.04, mol wt = 40,000), and dextran (B/P ratio = 0.09, mol wt = 70,000), exhibited no clear ordering based on size alone, and when dextrans of two different sizes (40,000 and 70,000 mol wt) were studied simultaneously, the relative amounts of the two dextran species in bile were the same as in perfusate. Taurocholate administration produced a 71% increase in bile flow but little or no (0-20%) increase in the output of horseradish peroxidase, microperoxidase, inulin, and dextran. Second, under nonsteady-state conditions in which the appearance in or disappearance from bile of selected markers was studied after their abrupt addition to or removal from perfusate, erythritol reached a B/P ratio of 1 within 2 min. Microperoxidase and dextran appeared in bile only after a lag period of 12 min and then slowly approached maximal values, whereas sucrose exhibited kinetically intermediate behavior. A similar pattern was observed after removal of >95% of the marker from the perfusate. Erythritol rapidly reapproached a B/P ratio of 1, whereas the B/P ratio for sucrose, dextran, and microperoxidase fell much more slowly and exceeded 1 for a full 30 min after perfusate washout. Finally, electron microscopy and fluorescence microscopy of cultured hepatocytes demonstrated the presence of horseradish peroxidase and fluoresceindextran, respectively, in intracellular vesicles, and fractionation of perfused liver homogenates revealed that at least 35-50% of sucrose, inulin, and dextran was associated with subcellular organelles.Collectively, these observations are most compatible with a transcytosis pathway that contributes minimally to the secretion of erythritol, but accounts for a substantial fraction of sucrose secretion and virtually all (>95%) of the blood-to-bile

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Section: Analytical and Preparative Techniquesmentioning

confidence: 99%

Section: Analytical and Preparative Techniquesmentioning

confidence: 99%

Section: Analytical and Preparative Techniquesmentioning

confidence: 99%

Section: Analytical and Preparative Techniquesmentioning

confidence: 99%

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Biliary secretion of fluid-phase markers by the isolated perfused rat liver. Role of transcellular vesicular transport.

et al. 1985

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“…For digitoxin also a strong inhibition of the cholate uptake by hepatocytes has been shown [48]. In contrast to taurocholate, cholate is taken up by hepatocytes predominantly by a sodium-independent transport system [49]. Ouabain, another neutral compound tested, did not affect LTE, uptake nor the transport of LTB4.…”

Section: Discuss I 0 Nmentioning

confidence: 97%

Leukotriene uptake by hepatocytes and hepatoma cells

Leier

Müller

Jedlitschky

et al. 1992

European Journal of Biochemistry

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The uptake of tritiated cysteinyl leukotrienes (LTC,, LTD,, LTE,) and LTB, was investigated in freshly isolated rat hepatocytes and different hepatoma cell lines under initial-rate conditions. Leukotriene uptake by hepatocytes was independent of an Na' gradient and a K + diffusion potential across the hepatocyte membranes as established in experiments with isolated hepatocytes and plasma membrane vesicles. Kinetic experiments with isolated hepatocytes indicated a low-K, system and a non-saturable system for the uptake of cysteinyl leukotrienes as well as LTB, under the conditions used. AS-30D hepatoma cells and human Hep G2 hepatoma cells were deficient in the uptake of cysteinyl leukotrienes, but showed significant accumulation of LTB,. Moreover, only LTB, was metabolized in Hep G2 hepatoma cells. Competition studies on the uptake of LTE4 and LTB, (10 nM each) indicated inhibition by the organic anions bromosulfophthalein, S-decyl glutathione, 4,4'-diisothiocyanato-stilbene-2,2'-disulfonate, probenecid, docosanedioate, and hexadecanedioate (100 pM each), but not by taurocholate, the amphiphilic cations verapamil and N-propyl ajmaline, and the neutral glycoside ouabain. Cholate and the glycoside digitoxin were inhibitors of LTB, uptake only. Bromosulfophthalein, the strongest inhibitor of leukotriene uptake by hepatocytes, did not inhibit LTB, uptake by Hep G2 hepatoma cells under the same experimental conditions.Leukotriene-binding proteins were analyzed by comparative photoaffinity labeling of human hepatocytes and Hep G2 hepatoma cells using [3H]LTE4 and [3H]LTB4 as the photolabile ligands. Predominant leukotriene-binding proteins with apparent molecular masses in the ranges of 48 -58 kDa and 38 -40 kDa were labeled by both leukotrienes in the particulate and in the cytosolic fraction of hepatocytes, respectively. In contrast, no labeling was obtained with [3H]LTE4 in Hep G2 cells. With ['HILTB, a protein with a molecular mass of about 48 kDa was predominantly labeled in the particulate fraction of the hepatoma cells, whereas in the cytosolic fraction a labeled protein in the range of 40 kDa was detected.Our results provide evidence for the existence of distinct uptake systems for cysteinyl leukotrienes and LTB4 at the sinusoidal membrane of hepatocytes; however, some of the inhibitors tested interfere with both transport systems. Only LTB,, but not cysteinyl leukotrienes, is taken up and metabolized by the transformed hepatoma cells.Effective elimination from the blood circulation and metabolic inactivation of leukotrienes are important for regulating the concentration of the biologically active mediators at their site of action. During its short half-life in the blood circulation, LTC, undergoes rapid intravascular metabolism yielding LTD, and LTE, [I -51. These cysteinyl leukotrienes are rapidly rcmoved from the circulation, predominantly by hepatocellular uptake and elimination [2-lo]. The liver is also a major site for the in vivo catabolism of LTB, [Ill. Catabolism of LTB4 was shown in granulocytes [12-...

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Bile Secretion and Cholestasis

Feranchak

2015

Yamada' S Textbook of Gastroenterology

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Effects of ion substitution on bile acid-dependent and -independent bile formation by rat liver.

Cited by 64 publications

References 69 publications

Biliary secretion of fluid-phase markers by the isolated perfused rat liver. Role of transcellular vesicular transport.

Biliary secretion of fluid-phase markers by the isolated perfused rat liver. Role of transcellular vesicular transport.

Leukotriene uptake by hepatocytes and hepatoma cells

Bile Secretion and Cholestasis

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