| First Author | Adella A | Year | 2024 |
| Journal | Pflugers Arch | PubMed ID | 39266724 |
| Mgi Jnum | J:358544 | Mgi Id | MGI:7764579 |
| Doi | 10.1007/s00424-024-03017-9 | Citation | Adella A, et al. (2024) Characterization of intestine-specific TRPM6 knockout C57BL/6 J mice: effects of short-term omeprazole treatment. Pflugers Arch |
| abstractText | The transient receptor potential melastatin type 6 (TRPM6) is a divalent cation channel pivotal for gatekeeping Mg(2+) balance. Disturbance in Mg(2+) balance has been associated with the chronic use of proton pump inhibitors (PPIs) such as omeprazole. In this study, we investigated if TRPM6 plays a role in mediating the effects of short-term (4 days) omeprazole treatment on intestinal Mg(2+) malabsorption using intestine-specific TRPM6 knockout (Vill1-TRPM6(-/-)) mice. To do this, forty-eight adult male C57BL/6 J mice (50% TRPM6(fl/fl) and 50% Vill1-TRPM6(-/-)) were characterized, and the distal colon of these mice was subjected to RNA sequencing. Moreover, these mice were exposed to 20 mg/kg bodyweight omeprazole or placebo for 4 days. Vill1-TRPM6(-/-) mice had a significantly lower (25)Mg(2+) absorption compared to control TRPM6(fl/fl) mice, accompanied by lower Mg(2+) serum levels, and urinary Mg(2+) excretion. Furthermore, renal Slc41a3, Trpm6, and Trpm7 gene expressions were higher in these animals, indicating a compensatory mechanism via the kidney. RNA sequencing of the distal colon revealed a downregulation of the Mn(2+) transporter Slc30a10. However, no changes in Mn(2+) serum, urine, and feces levels were observed. Moreover, 4 days omeprazole treatment did not affect Mg(2+) homeostasis as no changes in serum (25)Mg(2+) and total Mg(2+) were seen. In conclusion, we demonstrate here for the first time that Vill1-TRPM6(-/-) mice have a lower Mg(2+) absorption in the intestines. Moreover, short-term omeprazole treatment does not alter Mg(2+) absorption in both Vill1-TRPM6(-/-) and TRPM6(fl/fl) mice. This suggests that TRPM6-mediated Mg(2+) absorption in the intestines is not affected by short-term PPI administration. |
