| Theme |
Regulation, disease states and drug targets of kidney tubular transporters -- Topics |
| Title |
Magnesium transport via paracellular routes and associated diseases |
| Author |
Akira Ikari |
Department of Pharmaco−Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka |
| [ Summary ] |
Magnesium balance is controlled by absorption from the intestines, reabsorption from the kidneys, and its release from bone. Renal magnesium filtrated in the glomeruli is primarily reabsorbed in the thick ascending limb of Henle's loop. Mutations of claudin-16 and claudin-19 were found in patients with hypomagnesemia. Clau-din-16 and claudin-19 are tight junctional proteins and form divalent cations-permeable pores in the thick ascending limb of Henle's loop. Functional expression and mutational analysis of claudin-16 revealed that mutated claudin-16 was distributed in the cytosol, resulting in reduced magnesium permeability. Furthermore, the intracellular localization of claudin-16 was regulated by protein kinase A and extracellular-signal-regulated kinase. Hypomagnesemia may be involved in the onset and progression of lifestyle related diseases including hypertension and diabetes mellitus. In the future, we must elucidate the relation of changes in expression and intracellular localization of magnesium transporters to diseases. |