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Omeprazole enhances the colonic expression of the Mg(2+) transporter TRPM6.
MedLine Citation:
PMID:  23756852     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 μmol/24 h and 30 ± 4 μmol/24 h in omeprazole-treated and control mice, respectively), or fecal Mg(2+) excretion (84 ± 4 μmol/24 h and 76 ± 4 μmol/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-α), 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-α 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.
Authors:
A L L Lameris; M W Hess; I van Kruijsbergen; J G J Hoenderop; R J M Bindels
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-6-12
Journal Detail:
Title:  Pflugers Archiv : European journal of physiology     Volume:  -     ISSN:  1432-2013     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-6-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Physiology, Nijmegen Centre for Molecular Life Science, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
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