Elimination of asialofetuin and asialoorosomucoid by the intact rat. Quantitative aspects of the hepatic clearance mechanism.

The capacity of the liver to eliminate asialofetuin and asialoorosomucoid was investigated in intact rats. From plasma radioactivity curve measurements and assays on tissue homogenates the liver is shown to be able to dispose of an average of 19.8 microgram of asialofetuin/min per 100 g body weight. No other major route is identified for the disappearance of asialofetuin from the plasma, although trace amounts of the protein were detectable in the urine. From analyses of the plasma radioactivity curves the elimination process for asialoorosomucoid appears to be comparatively complex because of the existence of extrahepatic disposal routes. Quantification of labelled asialoorosomucoid in liver homogenates indicates, however, that the hepatic clearance rate for asialoorosomucoid is similar to that for asialofetuin. Urinary excretion significantly contributes to the disappearance of asialoorosomucoid from the plasma but the hepatic and renal routes do not account for all the protein lost from this compartment. At plasma concentrations above the maximal eliminative capacity of the liver, the hepatic clearance of asialofetuin obeys zero-order kinetics and is remarkably constant. Elimination of a quantity of asialoglycoprotein which exceeds the calculated total number of binding sites in the liver does not reduce the efficiency of the pathway, and studies of [3H]leucine incorporation indicate that the lectin, unlike the bound asialoglycoprotein, is not destroyed in the elimination process. Cytochalasin B (80 microgram/100 g body wt.) had no measureable effect on the hepatic clearance of asialofetuin. Administration of colchicine (10 mg/100 g body wt.) resulted in transitory accumulations of asialoorosomucoid in the liver, presumably due to interference with the intracellular transport of the endocytised protein.