AIM: To elucidate the effect and underlying mechanisms of omeprazole action on Mg2+ transport across the intestinal epithelium. METHODS: 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 Mg2+ 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 Mg2+ transport across the Caco-2 monolayers. RESULTS: Both apical to basolateral and basolateral to apical passive Mg2+ 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 Me 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 Mg2+ movement was impeded. CONCLUSION: Omeprazole decreased paracellular cation permeability and increased the activation energy for passive Mg2+ transport of Caco-2 monolayers that led to the suppression of passive Mg2+ absorption. (C) 2011 Baishideng. All rights reserved.
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Shanghai Univ Tradit Chinese Med, Pharmacokinet Lab, Shanghai 201203, Peoples R ChinaShanghai Univ Tradit Chinese Med, Pharmacokinet Lab, Shanghai 201203, Peoples R China
Shi, Rong
Zhong, Dafang
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Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Metab & Pharmacokinet Res, Shanghai 201203, Peoples R ChinaShanghai Univ Tradit Chinese Med, Pharmacokinet Lab, Shanghai 201203, Peoples R China
Zhong, Dafang
Ma, Yueming
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Shanghai Univ Tradit Chinese Med, Pharmacokinet Lab, Shanghai 201203, Peoples R ChinaShanghai Univ Tradit Chinese Med, Pharmacokinet Lab, Shanghai 201203, Peoples R China
Ma, Yueming
Liu, Yingying
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Shanghai Univ Tradit Chinese Med, Pharmacokinet Lab, Shanghai 201203, Peoples R ChinaShanghai Univ Tradit Chinese Med, Pharmacokinet Lab, Shanghai 201203, Peoples R China
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Millennium Pharmceut Inc, Drug Metab & Pharmacokinet, Drug Safety & Disposit, Cambridge, MA 02139 USAMillennium Pharmceut Inc, Drug Metab & Pharmacokinet, Drug Safety & Disposit, Cambridge, MA 02139 USA
Xia, CQ
Chuang, BC
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Millennium Pharmceut Inc, Drug Metab & Pharmacokinet, Drug Safety & Disposit, Cambridge, MA 02139 USAMillennium Pharmceut Inc, Drug Metab & Pharmacokinet, Drug Safety & Disposit, Cambridge, MA 02139 USA
Chuang, BC
Gallegos, R
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Millennium Pharmceut Inc, Drug Metab & Pharmacokinet, Drug Safety & Disposit, Cambridge, MA 02139 USAMillennium Pharmceut Inc, Drug Metab & Pharmacokinet, Drug Safety & Disposit, Cambridge, MA 02139 USA
Gallegos, R
Liu, N
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Millennium Pharmceut Inc, Drug Metab & Pharmacokinet, Drug Safety & Disposit, Cambridge, MA 02139 USAMillennium Pharmceut Inc, Drug Metab & Pharmacokinet, Drug Safety & Disposit, Cambridge, MA 02139 USA
Liu, N
Gan, LS
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Millennium Pharmceut Inc, Drug Metab & Pharmacokinet, Drug Safety & Disposit, Cambridge, MA 02139 USAMillennium Pharmceut Inc, Drug Metab & Pharmacokinet, Drug Safety & Disposit, Cambridge, MA 02139 USA
Gan, LS
Miwa, G
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Millennium Pharmceut Inc, Drug Metab & Pharmacokinet, Drug Safety & Disposit, Cambridge, MA 02139 USAMillennium Pharmceut Inc, Drug Metab & Pharmacokinet, Drug Safety & Disposit, Cambridge, MA 02139 USA