Article ; Online: Omeprazole enhances the colonic expression of the Mg(2+) transporter TRPM6.
Pflugers Archiv : European journal of physiology
2013 Volume 465, Issue 11, Page(s) 1613–1620
Abstract: ... the mRNA expression level of the transient receptor potential melastatin 6 (TRPM6), the predominant ... and low dietary Mg²⁺ availability. Omeprazole did not induce changes in serum Mg²⁺ levels (1.48 ± 0.05 ... and 1.54 ± 0.05 mmol/L in omeprazole-treated and control mice, respectively), urinary Mg²⁺ excretion ...
| Abstract | 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 Mg²⁺ leak, PPI-induced hypomagnesemia is hypothesized to result from intestinal malabsorption of Mg²⁺. 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 Mg²⁺ availability. Omeprazole did not induce changes in serum Mg²⁺ levels (1.48 ± 0.05 and 1.54 ± 0.05 mmol/L in omeprazole-treated and control mice, respectively), urinary Mg²⁺ excretion (35 ± 3 μmol/24 h and 30 ± 4 μmol/24 h in omeprazole-treated and control mice, respectively), or fecal Mg²⁺ 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 Mg²⁺ 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 Mg²⁺absorption is stimulated by extracellular protons, this would diminish the rate of intestinal Mg²⁺ absorption. The increase of TRPM6 expression in the colon may compensate for the reduced TRPM6 currents, thereby normalizing intestinal Mg²⁺ absorption during omeprazole treatment in C57BL/6J mice, explaining unchanged serum, urine, and fecal Mg²⁺ levels. |
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| MeSH term(s) | Animals ; Colon/drug effects ; Colon/metabolism ; H(+)-K(+)-Exchanging ATPase/genetics ; H(+)-K(+)-Exchanging ATPase/metabolism ; Homeostasis ; Intestinal Absorption/drug effects ; Magnesium/blood ; Magnesium/metabolism ; Magnesium/urine ; Mice ; Mice, Inbred C57BL ; Omeprazole/pharmacology ; Proton Pump Inhibitors/pharmacology ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; TRPM Cation Channels/genetics ; TRPM Cation Channels/metabolism ; Transcription, Genetic | |||||
| Chemical Substances | Proton Pump Inhibitors ; RNA, Messenger ; TRPM Cation Channels ; Trpm6 protein, mouse ; H(+)-K(+)-Exchanging ATPase (EC 3.6.3.10) ; Magnesium (I38ZP9992A) ; Omeprazole (KG60484QX9) | |||||
| Language | English | |||||
| Publishing date | 2013-06-12 | |||||
| Publishing country | Germany | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 6380-0 | |||||
| ISSN | 1432-2013 ; 0031-6768 | |||||
| ISSN (online) | 1432-2013 | |||||
| ISSN | 0031-6768 | |||||
| DOI | 10.1007/s00424-013-1306-0 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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