Cell volume and bile acid excretion

Abstract

The interaction between cell volume and taurocholate excretion into bile was studied in isolated perfused rat liver. Cell swelling due to hypo-osmotic exposure, addition of amino acids or insulin stimulated taurocholate excretion into bile and bile flow, whereas hyperosmotic cell shrinkage inhibited these. These effects were explained by changes in Vmax of taurocholate excretion into bile: Vmax. increased from about 300 to 700 nmol/min per g after cell swelling by 12-15% caused by either hypo-osmotic exposure or addition of amino acids under normo-osmotic conditions. Steady-state taurocholate excretion into bile was not affected when the influent K+ concentration was increased from 6 to 46 mM or decreased to 1 mM with iso-osmoticity being maintained by corresponding changes in the influent Na+ concentration. Replacement of 40 mM-NaCl by 80 mM-sucrose decreased taurocholate excretion into bile by about 70%; subsequent hypo-osmotic exposure by omission of sucrose increased taurocholate excretion to 160%. Only minor, statistically insignificant, effects of aniso-osmotic cell volume changes on the appearance of bolus-injected horseradish peroxidase in bile were observed. Taurocholate (400 microM) exhibited a cholestatic effect during hyperosmotic cell shrinkage, but not during hypo-osmotic cell swelling. Both taurocholate and tauroursodeoxycholate increased liver cell volume. Tauroursodeoxycholate stimulated taurocholate (100 microM) excretion into bile. This stimulatory effect was strongly dependent on the extent of tauroursodeoxycholate-induced cell swelling. During continuous infusion of taurocholate (100 microM) further addition of tauroursodeoxycholate at concentrations of 20, 50 and 100 microM increased cell volume by 10, 8 and 2% respectively, in parallel with a stimulation of taurocholate excretion into bile by 29, 27 and 9% respectively. There was a close relationship between the extent of cell volume changes and taurocholate excretion into bile, regardless of whether cell volume was modified by tauroursodeoxycholate, amino acids or aniso-osmotic exposure. The data suggest that: (i) liver cell volume is one important factor determining bile flow and biliary taurocholate excretion; (ii) swelling-induced stimulation of taurocholate excretion into bile is probably not explained by alterations of the membrane potential; (iii) bile acids modulate liver cell volume; (iv) taurocholate-induced cholestasis may depend on cell volume; (v) stimulation of taurocholate excretion into bile by tauroursodeoxycholate can largely be explained by tauroursodeoxycholate-induced cell swelling.

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

“…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.…”

“…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).…”

“…Interestingly, colchicine also markedly diminished the initial overshooting stimulation of taurocholate excretion into bile which is observed during the first 6 min of amino-acid addition. As shown recently, tauroursodeoxycholate at concentrations below 100 ,M induces cell swelling when added in addition to taurocholate (100 ,M) (Haussinger et al, 1992a), but not when added in the absence of taurocholate (C. Hallbrucker, S. vom Dahl and D. Hiiussinger, unpublished work). This tauroursodeoxycholate-induced cell swelling quantitatively explains the tauroursodeoxycholate-induced stimulation of taurocholate excretion into bile (Haussinger et al, 1992a).…”

“…As shown recently, tauroursodeoxycholate at concentrations below 100 ,M induces cell swelling when added in addition to taurocholate (100 ,M) (Haussinger et al, 1992a), but not when added in the absence of taurocholate (C. Hallbrucker, S. vom Dahl and D. Hiiussinger, unpublished work). This tauroursodeoxycholate-induced cell swelling quantitatively explains the tauroursodeoxycholate-induced stimulation of taurocholate excretion into bile (Haussinger et al, 1992a). As shown in Figure 5, in the presence of colchicine (5,M) the stimulatory action of tauroursodeoxycholate on taurocholate excretion was abolished.…”

“…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.…”