Current opinion on the regulation of small intestinal magnesium absorption

Figure 6 Mechanism of proton pump inhibitor-suppressed small intestinal magnesium absorption in proton pump inhibitor-induced hypomagnesemia rats. Proton pump inhibitor (PPI) suppresses membrane transient receptor potential melastatin 7 homodimer channel (TRPM7) and transient receptor potential melastatin 6/7 homodimer channel (TRPM6/7) expression but increases membrane transient receptor potential melastatin 6 homodimer channel (TRPM6) and cystathionine β-synthase domain divalent metal cation transport mediator 4 (CNNM4) expression. PPI induces phosphorylation of the T1851 residue and oxidation of the M1755 residue of the membrane TRPM6 channel, which reduces their channel permeability. These PPI effects reduce transcellular magnesium (Mg²⁺) absorption. Overexpression of claudin 2 (Cldn2), claudin 7 (Cldn7), claudin 12 (Cldn12), and claudin 15 (Cldn15) reduces paracellular permeability, which suppresses paracellular Mg²⁺ absorption. PPI also enhances P2Y₂- and acid-sensing ion-channel 1a (ASIC1a)-suppressed intestinal Mg²⁺ absorption. CFTR: Cystic fibrosis transmembrane conductance regulator; HCO₃⁻: Bicarbonate; NBCe1: Na⁺-HCO₃⁻ cotransporter-1.