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

Published online by Cambridge University Press:  09 March 2007

Michael W. Smith ,
K. Bhasker Shenoy ,
Edward S. Debnam ,
Michael R. Dashwood ,
Linda J. Churchill  and
S. Kaila Srai
Michael W. Smith
Affiliation:
Epithelial Transport Laboratories, Departments of Physiology, Royal Free and University College Medical School, London, UK
K. Bhasker Shenoy
Affiliation:
Epithelial Transport Laboratories, Departments of Physiology, Royal Free and University College Medical School, London, UK
Edward S. Debnam*
Affiliation:
Epithelial Transport Laboratories, Departments of Physiology, Royal Free and University College Medical School, London, UK
Michael R. Dashwood
Affiliation:
Epithelial Transport Laboratories, Departments of Chemical Pathology, Royal Free and University College Medical School, London, UK
Linda J. Churchill
Affiliation:
Epithelial Transport Laboratories, Departments of Physiology, Royal Free and University College Medical School, London, UK
S. Kaila Srai
Affiliation:
Epithelial Transport Laboratories, Departments of Biochemistry and Molecular Biology, Royal Free and University College Medical School, London, UK
*
*Corresponding author:Dr Edward S. Debnam, fax +44 20 7433 1921, email esdeb@rfc.ucl.ac.uk
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Abstract

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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.

Keywords

Intestinal iron transportDuodenumCadmium uptakeBrush border membrane
Type
Research Article
Information
British Journal of Nutrition , Volume 88 , Issue 1 , July 2002 , pp. 51 - 56
Copyright
Copyright © The Nutrition Society 2002

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