A kinetic study of hepatic uptake of canine intestinal alkaline phosphatase in the rat

This study describes the "plasma" disappearance and biliary excretion of injected purified canine intestinal alkaline phosphatase in the isolated perfused rat liver and in the intact rat. The plasma disappearance curve of the enzyme showed, apart from an initial rapid phase, a secondary phase, which may result from "exocytosis" of interiorized canine intestinal alkaline phosphatase into the circulation or from exhaustion of receptors involved in uptake of the enzyme during the process of endocytosis. A small fraction of the injected enzyme was found to be excreted into the bile and it was shown that there is a "kinetic" relationship between the biliary excretion pattern and the "plasma" disappearance of the enzyme. In addition, the effect of various sugars, sugar polymers and glycoproteins on plasma disappearance and biliary excretion of the enzyme was studied. Intravenous administration of galactose, lactose, galactan and especially asialofetuin prior to injection of canine intestinal alkaline phosphatase, resulted in inhibition of plasma disappearance of the enzyme, while the biliary excretion pattern of the enzyme was also changed. It is concluded that the rapid removal of injected canine intestinal alkaline phosphatase is predominantly, or even exclusively, achieved by the liver and that the hepatic uptake of the enzyme is most likely mediated by the "galactose-specific lectin" present on the plasma membrane of the hepatocytes.