TY - JOUR
T1 - Does Z‐Protein Have a Role in Transport of Bilirubin and Bromosulfophthalein by Isolated Perfused Rat Liver?
AU - Theilmann, Lorenz
AU - Stollman, Yacov R.
AU - Arias, Irwin M.
AU - Wolkoff, Allan W.
PY - 1984
Y1 - 1984
N2 - Bilirubin and other organic anions are transported in serum avidly bound to albumin from which they are extracted and transferred into the hepatocyte where they bind to cytosolic proteins. Two abundant organic anion binding proteins, ligandin and Z‐protein, were previously purified from liver cytosol and characterized. Other studies in isolated perfused rat liver revealed that selectively increased cytosolic ligandin concentration, following phenobarbital treatment or thyroidectomy, directly correlated with net bilirubin uptake which resulted from reduced bilirubin efflux. To clarify the role of Z‐protein in hepatic organic anion transport, we have now determined the kinetics of bilirubin and bromosulfophthalein (BSP) uptake in isolated perfused liver of normal rats and compared results to rats in which Z‐protein, but not ligandin, was selectively increased following treatment with clofibrate (ethylchlorophenoxy‐isobutyrate). These studies revealed that despite a 147% induction of Z‐protein in treated animals, there was no effect on influx or efflux of tracer doses of bilirubin or BSP. Addition of albumin to the protein‐free 10% fluorocarbon perfusate reduced influx of 3H‐bilirubin (p < 0.03) and tended to reduce influx of BSP. In this situation, there was still no influence of Z‐protein concentration on efflux. These studies indicate that Z‐protein does not appear to play a role in the hepatic uptake of bilirubin and BSP.
AB - Bilirubin and other organic anions are transported in serum avidly bound to albumin from which they are extracted and transferred into the hepatocyte where they bind to cytosolic proteins. Two abundant organic anion binding proteins, ligandin and Z‐protein, were previously purified from liver cytosol and characterized. Other studies in isolated perfused rat liver revealed that selectively increased cytosolic ligandin concentration, following phenobarbital treatment or thyroidectomy, directly correlated with net bilirubin uptake which resulted from reduced bilirubin efflux. To clarify the role of Z‐protein in hepatic organic anion transport, we have now determined the kinetics of bilirubin and bromosulfophthalein (BSP) uptake in isolated perfused liver of normal rats and compared results to rats in which Z‐protein, but not ligandin, was selectively increased following treatment with clofibrate (ethylchlorophenoxy‐isobutyrate). These studies revealed that despite a 147% induction of Z‐protein in treated animals, there was no effect on influx or efflux of tracer doses of bilirubin or BSP. Addition of albumin to the protein‐free 10% fluorocarbon perfusate reduced influx of 3H‐bilirubin (p < 0.03) and tended to reduce influx of BSP. In this situation, there was still no influence of Z‐protein concentration on efflux. These studies indicate that Z‐protein does not appear to play a role in the hepatic uptake of bilirubin and BSP.
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U2 - 10.1002/hep.1840040523
DO - 10.1002/hep.1840040523
M3 - Article
C2 - 6384000
AN - SCOPUS:0021142826
SN - 0270-9139
VL - 4
SP - 923
EP - 926
JO - Hepatology
JF - Hepatology
IS - 5
ER -