Divalent metal inhibition of non-haem iron uptake across the rat duodenal brush border membrane

Abstract

Duodenal Fe²⁺ uptake is essential to body Fe²⁺ homeostasis, but the interaction of metals with the uptake process remains unclear. The present study compared the effects of four essential trace metals (Mn²⁺, Zn²⁺, Co²⁺ and Ni²⁺) with two toxic metals (Pb²⁺ and Cd²⁺) on Fe²⁺ uptake across the brush border membrane of villus-attached duodenal enterocytes. Everted rat duodenum was exposed to buffer containing 0·2 mM-⁵⁹FE²⁺–ASCORBATE WITH OR WITHOUT THE COMPETING METAL (2 Mm) and the tissue was then processed for autoradiography allowing Fe²⁺ uptake to be determined at specific crypt–villus regions. The quantification method ensured that uptake by cells, rather than Fe²⁺ binding to the tissue surface, was measured. Fe²⁺ uptake was significantly inhibited by Cd²⁺ in upper villus enterocytes only and Pb²⁺ was without effect on Fe²⁺ uptake. The inhibition by Cd²⁺ was not due to general cell damage as judged by the release of lactate dehydrogenase from tissue into incubation fluid. Essential divalent trace metals reduced uptake significantly along the whole length of the crypt–villus axis. Cd²⁺ uptake, measured separately, took place at all regions of the villus–crypt axis, highest uptake being into crypt enterocytes. The very different uptake profiles for Cd²⁺ and Fe²⁺ suggests that the divalent metal transporter 1 is not the principal transporter of Cd²⁺. The addition of Fe²⁺ to incubation buffer inhibited Cd²⁺ uptake by both crypt and villus enterocytes. The possibility that the inhibitory actions of Fe²⁺ and Cd²⁺ on the uptakes of Cd²⁺ and Fe²⁺ respectively can be explained by a non-competitive action or the involvement of an additional metal transporter is discussed.