D. Hegner

Effect of Na on bile acid uptake by isolated rat hepatocytes. Evidence for a heterogeneous system.

The effect of Na on cholate and taurocholate uptake was studied in isolated rat hepatocytes. Uptake of both bile acids can be divided into three components: a) a non-saturable component independent of Na, b) a Na-independent saturable and c) a Na-dependent saturable component. The two saturable components were inhibited by KCN, oligomycin and various other bile acids, which suggests carrier-mediated, energy-requiring processes. The relationship between Na concentration and the Na-dependent uptake rate was sigmoidal. The maximal uptake rate, rather than the Km, was affected by Na. These results suggest that more than one Na (probably two) are cosubstrates in the transport of one bile acid molecule and Na exerts a stimulatory effect on the translocation of the bile acid-carrier complex across the membranes. The Na-dependent uptake was inhibited by ouabain, suggesting that this uptake process is linked to the activity of membrane bound (Na-K)ATPase. Inhibition and competition studies suggest that cholate and taurocholate share a common Na-independent transport system while there are at least two Na-dependent transport systems for taurocholate, one of which is shared by cholate.

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

Abstract Cholate and taurocholate uptakes were studied in presence of albumin using isolated rat hepatocytes. Albumin decreased nonspecific binding of both bile acids and inhibited cholate uptake noncompetitively and taurocholate uptake competitively. Although different bile acids except dehydrocholate inhibited both cholate and taurocholate uptake, their relative inhibitory potency was not the same for both bile acids. Uptake of both bile acids was characterized by a saturable as well as an unsaturable process both in presence and in absence of albumin. The results suggest that both bile acids may be transported by more than one carrier and taurocholate is transported more efficiently than cholate by hepatocytes.

Bile acids secretion and synthesis by isolated rat hepatocytes

Abstract Bile acids secretion and their distribution were studied in isolated rat hepatocytes. Bile acids secretion was linearly related with time for first three hours of incubation and the net secretion rate was 23.2 ± 2.74 nmoles per g cells (wet weight) per minute. Isolated hepatocytes synthesized relatively more chenodeoxycholic acid than cholic acid compared to whole animal. These results suggest that isolated hepatocytes synthesize and secrete bile acids and thus provide experimental system to study the effect of drugs on bile acids secretion and synthesis at cellular level.

The lack of active bile acid transport in AS-30 D ascites hepatoma cells.

SummaryThe uptake of cholic acid as well as taurocholic acid into AS-30 D ascites hepatoma cells showed linearity with respect to incubation concentrations. It has been suggested that these processes can be described as simple diffusion. In further experiments it could be shown that ascites hepatoma cells were unable to conjugate cholic acid. These results may have significance in the phalloidin action on hepatocytes.

Inhibition of hepatic uptake of bile acids by rifamycins.

SummaryThe effect of rifamycin SV and rifampicin on hepatic bile acid uptake was studied using isolated rat hepatocytes in presence and in absence of albumin. The drugs inhibited cholate uptake more than taurocholate uptake and the inhibition was of non-competitive type. In presence of 3% albumin the inhibitory effect of the drugs was more for cholate and less for taurocholate uptake than in absence of albumin. Neither the binding of bile acids nor that of the drugs to albumin was altered by one another. Thus the effect in presence of albumin cannot be explained by the binding of the drugs and bile acids to albumin alone. It is suggested that albumin interacts with hepatic bile acid uptake process and this interaction with cholate uptake is different from that with taurocholate uptake. This additional and different effect of albumin may explain the effect of the drugs in presence of albumin. The results may be of clinical significance in rifamycins treatments.

Interaction of fusidates with bile acid uptake by isolated rat hepatocytes

SummaryThe interaction of fusidic acid and two of its conjugates with carrier-mediated uptake of bile acids was investigated in isolated rat hepatocytes. All three fusidates inhibited the uptake of both cholate and taurocholate competitively suggesting a direct interaction of fusidates with bile acid carrier. The inhibition constants for all three fusidates for the inhibition of cholate uptake were significantly different from the respective inhibition constants for the inhibition of taurocholate uptake. This would indicate that both cholate and taurocholate are transported by more than one carrier into hepatocytes. The results may also indicate that taurine conjugated bile acids may be transported preferentially by one transport system while unconjugated bile acids may be preferentially transported by another transport system.

Effects of Concanavalin A on the isolated perfused rat liver

SummaryIn the isolated perfused liver, Concanavalin A provoked a significant decrease of flow rate within 2 to 4 min which was dose-dependent and could be partly inhibited by specific antagonists.Furthermore it was found that the lectin led to a decline of the respiration, an increase of the lactate/pyruvate ratio and a release of the transaminases into the medium. It was suggested that Concanavalin A displaced endothelial cells in the liver capillaries, which occluded the vessels and decreased the flow rate. The decreased respiration was considered to be secondary to this effect.