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Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Pflugers+Arch 2013 ; 465 (11): 1613-20 Nephropedia Template TP
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Omeprazole enhances the colonic expression of the Mg(2+) transporter TRPM6 #MMPMID23756852
Pflugers Arch 2013[Nov]; 465 (11): 1613-20 PMID23756852show ga
Proton pump inhibitors (PPIs) are potent blockers of gastric acid secretion, used by millions of patients suffering from gastric acid-related complaints. Although PPIs have an excellent safety profile, an increasing number of case reports describe patients with severe hypomagnesemia due to long-term PPI use. As there is no evidence of a renal Mg(2)(+) leak, PPI-induced hypomagnesemia is hypothesized to result from intestinal malabsorption of Mg(2)(+). The aim of this study was to investigate the effect of PPIs on Mg (2)(+)homeostasis in an in vivo mouse model. To this end, C57BL/6J mice were treated with omeprazole, under normal and low dietary Mg(2)(+) availability. Omeprazole did not induce changes in serum Mg(2)(+) levels (1.48 +/- 0.05 and 1.54 +/- 0.05 mmol/L in omeprazole-treated and control mice, respectively), urinary Mg(2)(+) excretion (35 +/- 3 mumol/24 h and 30 +/- 4 mumol/24 h in omeprazole-treated and control mice, respectively), or fecal Mg(2)(+) excretion (84 +/- 4 mumol/24 h and 76 +/- 4 mumol/24 h in omeprazole-treated and control mice, respectively) under any of the tested experimental conditions. However, omeprazole treatment did increase the mRNA expression level of the transient receptor potential melastatin 6 (TRPM6), the predominant intestinal Mg(2)(+) channel, in the colon (167 +/- 15 and 100 +/- 7 % in omeprazole-treated and control mice, respectively, P < 0.05). In addition, the expression of the colonic H(+),K(+)-ATPase (cHK-alpha), a homolog of the gastric H(+),K(+)-ATPase that is the primary target of omeprazole, was also significantly increased (354 +/- 43 and 100 +/- 24 % in omeprazole-treated and control mice, respectively, P < 0.05). The expression levels of other magnesiotropic genes remained unchanged. Based on these findings, we hypothesize that omeprazole inhibits cHK-alpha activity, resulting in reduced extrusion of protons into the large intestine. Since TRPM6-mediated Mg(2)(+)absorption is stimulated by extracellular protons, this would diminish the rate of intestinal Mg(2)(+) absorption. The increase of TRPM6 expression in the colon may compensate for the reduced TRPM6 currents, thereby normalizing intestinal Mg(2)(+) absorption during omeprazole treatment in C57BL/6J mice, explaining unchanged serum, urine, and fecal Mg(2)(+) levels.
Pflugers+Arch 2013 ; 465 (11): 1613-20
