Enhancement of hepatic gallium-67 uptake by asialo-transferrin.
A significant fraction of intravenously injected 67Ga localizes in the liver. The mechanism of 67Ga uptake by the liver is not clear. Hepatocyte membranes contain galactose-specific receptors which selectively remove asialo-glycoproteins from the circulation by way of endocytosis. In this investigation, we examined whether endocytic uptake of asialo-transferrin would involve 67Ga transport into hepatocytes. We demonstrated that asialo-transferrin bound 67Ga as effectively as apotransferrin. Human asialo-transferrin markedly enhanced 67Ga uptake by isolated, perfused rat livers. Human asialo-orosomucoid, but not orosomucoid competitively inhibited hepatic uptake of the 67Ga asialo-transferrin complex, indicating that hepatic 67Ga uptake in the presence of asialo-transferrin occurred by way of galactose-specific receptors. Our results point to a novel pathway for metal ion transport into hepatocytes by way of galactose receptor mediated endocytosis.
D000818:Animals; D001059:Apoproteins / Q000378:metabolism; D001212:Asialoglycoproteins; D001646:Bile / Q000378:metabolism; D001692:Biological Transport; D004705:Endocytosis; D005710:Gallium Radioisotopes / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D009961:Orosomucoid / Q000031:analogs & derivatives / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology; D014168:Transferrin / Q000031:analogs & derivatives* / Q000378:metabolism
D001059:Apoproteins; D001212:Asialoglycoproteins; D005710:Gallium Radioisotopes; D009961:Orosomucoid; D011956:Receptors, Cell Surface; D014168:Transferrin; C017030:asialoorosomucoid; C017031:asialotransferrins; C039707:galactose receptor