Omeprazole decreases magnesium transport across Caco-2 monolayers

Abstract

To elucidate the effect and underlying mechanisms of omeprazole action on Mg(2+) transport across the intestinal epithelium. Caco-2 monolayers were cultured in various dose omeprazole-containing media for 14 or 21 d before being inserted into a modified Ussing chamber apparatus to investigate the bi-directional Mg(2+) transport and electrical parameters. Paracellular permeability of the monolayer was also observed by the dilution potential technique and a cation permeability study. An Arrhenius plot was performed to elucidate the activation energy of passive Mg(2+) transport across the Caco-2 monolayers. Both apical to basolateral and basolateral to apical passive Mg(2+) fluxes of omeprazole-treated epithelium were decreased in a dose- and time-dependent manner. Omeprazole also decreased the paracellular cation selectivity and changed the paracellular selective permeability profile of Caco-2 epithelium to Li(+), Na(+), K(+), Rb(+), and Cs(+) from series VII to series VI of the Eisenman sequence. The Arrhenius plot revealed the higher activation energy for passive Mg(2+) transport in omeprazole-treated epithelium than that of control epithelium, indicating that omeprazole affected the paracellular channel of Caco-2 epithelium in such a way that Mg(2+) movement was impeded. Omeprazole decreased paracellular cation permeability and increased the activation energy for passive Mg(2+) transport of Caco-2 monolayers that led to the suppression of passive Mg(2+) absorption.