Hepatic uptake of unbound radio-B12 and radio-B12 bound to various B12 binders was studied in 48 rats using a method of in situ liver perfusion of homologous whole blood without recirculation. Compared with unbound radio-B12, radio-B12 bound to pernicious anemia gastric juice, human saliva, hog intrinsic factor concentrate, and boiled hog intrinsic factor concentrate increased uptake of B12 by rat liver. B12 bound to normal human gastric juice, however, was removed in a manner quantitatively similar to that observed with unbound B12.

Depression of reticuloendothelial system activity by india ink injection prior to perfusion of hog intrinsic factor concentrate-bound B12 did not significantly alter hepatic B12 removal rates. Comparison with results obtained in similar experiments, but without prior reticuloendothelial system depression, suggests that the removal process was accomplished by hepatic parenchymal cells rather than reticuloendothelial cells of the liver.

These results suggest that B12 binders of hog intrinsic factor concentrate, pernicious anemia gastric juice, and saliva may function in the membrane transport of B12 in the liver in a manner both quantitatively and qualitatively different from those of serum. This transport function is obviously not limited to intrinsic factor, since materials with and without intrinsic factor activity can produce this effect.

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