Studies on Human Gastric Intrinsic Factor OBSERVATIONS ON ITS POSSIBLE ABSORPTION AND ENTEROHEPATIC CIRCULATION

Under physiological conditions Intrinsic Factor secreted by the cells of the gastric mucosa is required for the uptake of vitamin B12 by the small intestine. Vitamin B12 passes to the blood, reaches the liver as well as other organs, and some is re‐excreted into the bile (Grasbeck, Nyberg and Reizenstein, 1958). Whether vitamin B12 is accompanied by Intrinsic Factor on its passage into the blood and into the bile or whether Intrinsic Factor does not pass beyond the intestinal wall is uncertain. Miller and Hunter (1957) have demonstrated that not only does Intrinsic Factor enhance the vitamin B12 uptake by gut but it will also promote the attachment of vitamin B12 to serum, liver, kidney and other tissues. It has been suggested that vitamin B12 and Intrinsic Factor, but not vitamin B12 alone, is required to restore normoblastic haemopoiesis in a culture of megaloblastic marrow (Lajtha, 1950; Callender and Lajtha, 1951; Pendl, Franz and Hunkel‐Trees, 1958). Toporek (1961) has shown that Intrinsic Factor perfused through a rat liver is re‐excreted in an active form into the bile and Herbert and Kaplan (1961) have reported evidence suggesting that Intrinsic Factor, like vitamin B12 (Grasbeck et al., 1958) takes part in an entero‐hepatic circulation. Further Gulberg and Kistner (1963) have found that hog bile contains a fraction showing the same immunological behaviour as the main vitamin B12 binding component of hog Intrinsic Factor. It is likely that the haematological relapse of patients with pernicious anaemia treated with oral vitamin B12 and hog Intrinsic Factor preparations is due to the development of antibodies against hog Intrinsic Factor suggesting absorption of at least some of this material (Schwartz, 1962). On the other hand, Cooper and Castle (1960) found evidence for the release of vitamin B12 from Intrinsic Factor at the gut wall. Taylor and Medenica (1962) found that the uptake of vitamin B12 by rat tissues, particularly the liver, was independent of a source of Intrinsic Factor and others have failed to substantiate an Intrinsic Factor requirement for the maturation of a megaloblastic marrow culture (Reisner and Swan, 1954; Carrara, Taglioretti and Eridani, 1960). The large molecular weight suggested for Intrinsic Factor by some workers (Bromer and Davisson, 1961) does not favour its transport beyond the gut wall, at least in the undegraded form. The purpose of the present study was, firstly, to obtain evidence for or against transport of Intrinsic Factor into the blood and, secondly, to determine whether Intrinsic Factor, like vitamin B12, takes part in an entero‐hepatic circulation.