Intrinsic factor-cobalamin accumulates in the ilea of mice treated with chloroquine.

Chloroquine, which interferes with the degradation of a number of transport proteins, impedes the exit of cobalamin from the small intestine of the mouse. This study was designed to determine if treatment with the drug led to the retention of cobalamin in the form of intrinsic factor-cobalamin in the ileal mucosa. Solubilized homogenates were prepared 2-4 h after an oral dose of [57Co]cobalamin and were examined by gel chromatography. There was a progressive transfer of [57Co]cobalamin from a protein identified as intrinsic factor to transcobalamin II in control mice. In chloroquine-treated mice, the major radioactive protein peak 2-4 h after an oral dose corresponded with the position of intrinsic factor. Only a small amount of the radioactivity was associated with transcobalamin. Cobalamin binding proteins were also identified by polyacrylamide gel electrophoresis and by their reaction with specific antibodies. It is concluded that chloroquine interferes with the release of cobalamin from intrinsic factor and thus slows the release of cobalamin from the intestine.