Cell swelling increases bile flow and taurocholate excretion into bile in isolated perfused rat liver

Hallbrucker, Christian; Läng, Florian; Gerok, W.; Häussinger, Dieter

doi:10.1042/bj2810593

Cited by 45 publications

(35 citation statements)

References 15 publications

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“…After a 50 min normotonic perfusion with taurocholate (100 #uM), LDH activity in effluent perfusate was 6 + 1 units/l (n = 6) and was 11 + 1 units/i (n = 3) when colchicine (5 #M) was present between 20 and 50 min of taurocholate infusion. Corresponding Effect of coichicine on taurocholate excretion into bile As shown in Figure 2, and in line with previous data (Hallbrucker et al, 1992;Haiussinger et al, 1992a), taurocholate (100 ,uM) excretion into bile was significantly higher in hypotonic (225 mosmol/l) than in normotonic (305 mosmol/l) perfusions. This effect was observed throughout an 80 min perfusion period (not shown, but for the constancy of taurocholate excretion over a 100 min normotonic perfusion period in the absence of colchicine; see Figure 3 below).…”

Section: Methodssupporting

confidence: 91%

“…Coichicine abolishes the cell-swelling-induced stimulation of taurocholate excretion into bile As shown in Figure 3, cell swelling due to hypotonic (225 mosmol/l) exposure stimulated taurocholate excretion into bile and bile flow, in line with previous results (Hallbrucker et al, 1992;Haussinger et al, 1992a). When, however, hypotonic exposure was instituted 20 min after onset of colchicine infusion, i.e.…”

Section: Methodssupporting

confidence: 89%

“…Effect of coichicine on the inhibition of taurocholate excretion into bile after cell shrinkage As shown recently, hypertonic (385 mosmol/l) cell shrinkage inhibits taurocholate excretion into bile (Hallbrucker et al, 1992;Haussinger et al, 1992a). A persistent (about 35 %) inhibition was also observed when lumicolchicine (5 ,uM) was added 20-25 min before hypertonic exposure; this effect was fully reversible upon normotonic re-exposure ( Figure 6).…”

Section: Methodssupporting

confidence: 61%

“…Effect of coichicine on the swelling-induced stimulation of 14CO2 (Haussinger et al, 1992b) and [1-14C]glucose (Saha et al, 1992). As shown in (Haussinger et al, 1992b) or the swelling-induced stimulation of pentose-phosphate-cycle flux (Saha et al, 1992 (Hallbrucker et al, 1992;Haussinger et al, 1992a) in response to cell swelling/shrinkage may reflect cell-volume effects on canalicular bile-acid secretion. The present findings support the previous speculation that cell swelling leads to a rapid insertion into the canalicular membrane of intracellularly stored bile-acid transporter molecules Haussinger et al, 1992a), which have been identified recently as primary active, i.e.…”

Section: Methodsmentioning

confidence: 94%

“…Cell swelling, induced by either hypotonic exposure or addition of amino acids, insulin or tauroursodeoxycholate, increases the Vmax of transcellular taurocholate transport in perfused rat liver within minutes, whereas hypertonic cell shrinkage decreases transport capacity (Hallbrucker et al, 1992;Haussinger et al, 1992a). However, the underlying mechanism remained unclear.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver

Häussinger

Saha

Hallbrucker

et al. 1993

Biochemical Journal

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101

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An increase of the hepatocellular hydratation state, induced by hypotonic exposure, amino acids or tauroursodeoxycholate, was shown to increase within minutes the Vmax of transcellular taurocholate transport and excretion into bile [Häussinger, Hallbrucker, Saha, Lang and Gerok (1992) Biochem. J. 288, 681-689]. This stimulatory effect of cell swelling on taurocholate excretion into bile is abolished in the presence of colchicine (5 microM). On the other hand, colchicine did not affect the stimulatory action of hypotonic cell swelling on 14CO2 production from [1-14C]glycine or [1-14C]glucose. Likewise, volume regulatory K+ fluxes following anisotonic exposure were not influenced in the presence of colchicine. Lumicolchicine (5 microM), a stereoisomer of colchicine without an inhibitory effect on microtubules, did not abolish the stimulation of taurocholate excretion into bile following hypo-osmotic exposure. Hypertonic cell shrinkage decreased taurocholate excretion into bile by about 35%; this effect was fully reversible upon normotonic re-exposure. With colchicine pretreatment, however, the hypertonicity-induced inhibition of taurocholate excretion was blunted and was no longer reversible upon normotonic re-exposure. The results suggest that stimulation of taurocholate excretion into bile in response to cell swelling involves a colchicine-sensitive, probably microtubule-dependent, mechanism, but not the stimulation of other cell-volume-sensitive pathways such as glycine oxidation or the pentose-phosphate shunt. It is hypothesized that the swelling-induced stimulation of taurocholate excretion into bile is due to a microtubule-dependent insertion of bile acid transporter molecules into the canalicular membrane.

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Section: Methodssupporting

confidence: 91%

Section: Methodssupporting

confidence: 89%

Section: Methodssupporting

confidence: 61%

Section: Methodsmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver

Häussinger

Saha

Hallbrucker

et al. 1993

Biochemical Journal

Self Cite

101

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Hormone-induced bile flow and hepatobiliary calcium fluxes are attenuated in the perfused liver of rats made cholestatic with ethynylestradiolin vivo and with phalloidinin vitro

1995

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The actions of vasopressin and glucagon, administered alone or together, were assessed on bile flow in perfused livers from rats made cholestatic by the injection of ethynylestradiol and from those allowed to recover from such treatment. Concomitant measurements were made of biliary calcium output as well as changes in the perfusate Ca2+ concentration, glucose output, and oxygen uptake. Experiments were also conducted where cholestasis was induced in vitro in the perfused liver by the infusion of phalloidin. In each case cholestasis was demonstrated to have occurred by a reduction in bile flow by approximately 50%. The data show that the transient increase in bile flow and bile calcium seen in control rat liver soon after the administration of vasopressin, particularly when coadministered with glucagon, is largely absent in cholestasis induced by ethynylestradiol and attenuated in cholestasis induced by phalloidin. At the same time the pattern of perfusate Ca2+ fluxes in ethynylestradiol-induced cholestasis shifts to one reflecting net efflux of the ion from the liver. The responses to glucagon administration alone contrast with those of vasopressin in that in the perfused liver of ethynylestradiol-treated rats, glucagon induces a pronounced and sustained increase in bile flow. In cholestasis induced by both ethynylestradiol and phalloidin, glucagon fails to induce an initial transient decrease in bile flow. The effects of glucagon, including enhancement of vasopressin-stimulated bile flow in control and in ethynylestradiol-treated rats, can be mimicked by dibutyryl cyclic adenosine monophosphate (cAMP). Changes in glucose output and oxygen uptake induced by both hormones are only slightly attenuated. The data show that the modulation of bile flow that occurs rapidly after the administration of vasopressin and glucagon to control perfused rat liver is altered in conditions of cholestasis induced by either ethynylestradiol or phalloidin.

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Redistribution of canalicular organic anion transport activity in isolated and cultured rat hepatocytes

Roelofsen¹,

Bakker²,

Schoemaker³

et al. 1995

Hepatology

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The hepatocanalicular transport of a large number of organic anions, such as bilirubin glucuronides and glutathione conjugates in the rat, is mediated by an adenosine triphosphate (ATP)-dependent transport system, which is termed canalicular multispecific organic anion transporter (cMOAT). This system is mainly defined by its deficiency in mutant TR rats. We have previously reported that in cultured hepatocytes the fluorescent organic anion glutathione-bimane (GS-B) accumulates in intracellular vesicles and that this transport is mediated by cMOAT. We now show that this intracellular accumulation of fluorescent organic anion is largely absent in freshly isolated hepatocytes but appears when cells are incubated in suspension at 37 degrees C or cultured for periods of 1 to 24 hours. The appearance of intracellular cMOAT activity coincides with the disappearance of 70% of cMOAT activity from the plasma membrane as measured by the transport activity of the cells for the organic anion dinitrophenyl-glutathione (GS-DNP). Both the appearance of intracellular cMOAT and the disappearance of transport activity from the plasma membrane were completely inhibited at temperatures below 20 degrees C. Residual cMOAT activity in 24-hour cultured hepatocytes could be further diminished by incubation of the cells with 1 mumol/L monensin or 10 mmol/L methylamine. We conclude that after disruption of the cell polarity by collagenase isolation of the hepatocytes, remnants of apical membrane containing cMOAT are rapidly endocytosed when the cells are kept at 37 degrees C. Evidence suggests that at least part of the transporters may recycle back to the plasma membrane after endocytosis. These observations may be relevant for the understanding of regulation of canalicular transport.

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Cell swelling increases bile flow and taurocholate excretion into bile in isolated perfused rat liver

Cited by 45 publications

References 15 publications

Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver

Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver

Hormone-induced bile flow and hepatobiliary calcium fluxes are attenuated in the perfused liver of rats made cholestatic with ethynylestradiolin vivo and with phalloidinin vitro

Redistribution of canalicular organic anion transport activity in isolated and cultured rat hepatocytes

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