Inositol Phosphates Inhibit Uptake and Transport of Iron and Zinc by a Human Intestinal Cell Line , ,

Abstract

To examine the influence of inositol phosphates on the uptake and absorption of Fe and Zn, Caco-2 cells were grown on either plastic (uptake studies) or porous membranes in bicameral chambers (transport/absorption studies). Caco-2, a human colon adenocarcinoma cell line, was selected as the test cell because it spontaneously differentiates into polarized enterocyte-like cells at confluency. Uptake of Fe (added as Fenitrilotriacetate complex) from a calcium-free solution by fully differentiated cells was 37 pmol/cm². Addition of 10-fold molar excess of individual inositol phosphates (IP₃, IP₄, IP₅ or IP₆) decreased Fe solubility by 13 to 25% and reduced Fe uptake by 50 to 65%. The rate of transport of Fe from the apical solution into the basolateral chamber [1.4 ± 0.1 pmol/(h·cm²)] decreased (34–96%) in proportion to the degree of phosphorylation of the inositol derivative in the apical compartment. Uptake and transepithelial transport of Zn were 246 ± 5 pmol/cm² and 23 ± 1 pmol/(h·cm²), respectively. The solubility, uptake and rate of transport of Zn also decreased in proportion to the degree of phosphorylation of inositol. These results demonstrate the inhibitory influence of IP₃–IP₆ on the uptake and transport of Fe and Zn and support the usefulness of the Caco-2 human cell line as an appropriate model for evaluating the effects of specific dietary factors on trace metal bioavailability.