Current opinion on the regulation of small intestinal magnesium absorption

Magnesium(Mg^(2+))has an important role in numerous biological functions,and Mg^(2+)deficiency is associated with several diseases.Therefore,adequate intestinal absorption of Mg^(2+)is vital for health.The small intestine was previously thought to absorb digested Mg^(2+)exclusively through an unregulated paracellular mechanism,which is responsible for approximately 90%of total Mg^(2+)absorption.Recent studies,however,have revealed that the duodenum,jejunum,and ileum absorb Mg^(2+)through both transcellular and paracellular routes.Several regulatory factors of small intestinal Mg^(2+)uptake also have been explored,e.g.,parathyroid hormone,fibroblast growth factor-23,apical acidity,proton pump inhibitor,and pH-sensing channel and receptors.The mechanistic factors underlying proton pump inhibitor suppression of small intestinal Mg^(2+),such as magnesiotropic protein dysfunction,higher mucosal bicarbonate secretion,Paneth cell dysfunction,and intestinal inflammation,are currently being explored.The potential role of small intestinal microbiomes in Mg^(2+)absorption has also been proposed.In this article,we reviewed the current knowledge on the mechanisms and regulatory factors of small intestinal Mg^(2+)absorption.

Omeprazole decreases magnesium transport across Caco-2 monolayers

AIM:To elucidate the effect and underlying mechanisms of omeprazole action on Mg 2+ 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 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.RESULTS: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 seriesⅦto seriesⅥof the Eisenman sequence.The Arrhenius plot revealed the higher activation energy for passive Mg 2+ transport in omeprazoletreated 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.CONCLUSION: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.

Effect of prolonged omeprazole administration on segmental intestinal Mg2+ absorption in male Sprague-Dawley rats

BACKGROUND The exact mechanism of proton pump inhibitors(PPIs)-induced hypomagnesemia(PPIH) is largely unknown. Previous studies proposed that PPIH is a consequence of intestinal Mg2+ malabsorption. However, the mechanism of PPIs-suppressed intestinal Mg2+ absorption is under debate.AIM To investigate the effect of 12-wk and 24-wk omeprazole injection on the total,transcellular, and paracellular Mg2+ absorption in the duodenum, jejunum, ileum,and colon of male Sprague-Dawley rats.METHODS The rats received 20 mg/kg·d subcutaneous omeprazole injection for 12 or 24 wk.Plasma and urinary Mg2+, Ca2+, and PO43-levels were measured. The plasma concentrations of 1α,25-dihydroxyvitamin D3(1α,25(OH)2D3), parathyroid hormone(PTH), fibroblast growth factor 23(FGF-23), epidermal growth factor(EGF), and insulin were also observed. The duodenum, jejunum, ileum, and colon of each rat were mounted onto individual modified Using chamber setups to study the rates of total, transcellular, and paracellular Mg2+ absorption simultaneously. The expression of transient receptor potential melastatin 6(TRPM6) and cyclin M4(CNNM4) in the entire intestinal tract was also measured.RESULTS Single-dose omeprazole injection significantly increased the intraluminal p H of the stomach, duodenum, and jejunum. Omeprazole injection for 12 and 24 wk induced hypomagnesemia with reduced urinary Mg2+ excretion. The plasma Ca2+ was normal but the urinary Ca2+ excretion was reduced in rats with PPIH. The plasma and urinary PO43-levels increased in PPIH rats. The levels of1α,25(OH)2D3 and FGF-23 increased, whereas that of plasma EGF decreased in the omeprazole-treated rats. The rates of the total, transcellular, and paracellular Mg2+ absorption was significantly lower in the duodenum, jejunum, ileum, and colon of the rats with PPIH than in those of the control rats. The percent suppression of Mg2+ absorption in the duodenum, jejunum, ileum, and colon of the rats with PPIH compared with the control rats was 81.86%, 70.59%, 69.45%,and 39.25%, respectively. Compared with the control rats, the rats with PPIH had significantly higher TRPM6 and CNNM4 expression levels throughout the intestinal tract.CONCLUSION Intestinal Mg2+ malabsorption was observed throughout the intestinal tract of rats with PPIH. PPIs mainly suppressed small intestinal Mg2+ absorption. Omeprazole exerted no effect on the intraluminal acidic pH in the colon. Thus, the lowest percent suppression of total Mg2+ absorption was found in the colon. The expression levels of TRPM6 and CNNM4 increased, indicating the presence of a compensatory response to Mg2+ malabsorption in rats with PPIH. Therefore, the small intestine is an appropriate segment that should be modulated to counteract PPIH.