title: [Lithium and its relation with the epithelial sodium channel and aquaporin-2].
abstract: For more than 40 years lithium has been used to treat bipolar disorder and recent trials suggest a potential efficacy also in the treatment of the amnestic mild cognitive impairment. Lithium is filtered by the glomerulus and 65% - 75% of the filtered amount is reabsorbed along the proximal tubule and in the thick ascending limb of Henle's loop by the Na+, K+, 2Cl- transporter and via paracellular. A small fraction of lithium is reabsorbed in the collecting duct's principal cells through the epithelial Na channel (ENaC) located on the apical side of the cells. Polyuria, renal tubular acidosis and chronic renal failure are the most frequent adverse effects of lithium after 10-20 years of treatment and these alterations can reach to a vasopressin nonresponding form of diabetes insipidus entity called nephrogenic diabetes insipidus. It is believed that the molecular mechanisms of these renal changes are related to a reduction in the number of aquaporin-2 inserted in the apical membrane of the cells. The causes of this are complex. Lithium is a powerful inhibitor of the enzyme glycogen synthase kinase 3β and this is associated with a lower activity of adenylate cyclase with a reduction in the cAMP levels inside of the cells. The latter may interfere with the synthesis of aquaporin-2 and also with the traffic of these molecules from the subapical site to membrane promoting the impairment of water reabsorption in the distal part of the kidney.
authors.affiliation: Laboratorio de Canales Iónicos, Instituto de Investigaciones Médicas Alfredo Lanari, Universidad de Buenos Aires, IDIM-CONICET, Argentina. lgalizia@gmail.com
authors.forename: Luciano
authors.initials: L
authors.lastname: Galizia
authors.forename: Gabriela I
authors.initials: GI
authors.lastname: Marino
authors.forename: Basilio A
authors.initials: BA
authors.lastname: Kotsias
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D051399:Aquaporin 2 / Q000502:physiology*; D001714:Bipolar Disorder / Q000188:drug therapy; D018500:Diabetes Insipidus, Nephrogenic / Q000139:chemically induced; D053503:Epithelial Sodium Channels / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000503:physiopathology; D008094:Lithium / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D018020:Lithium Compounds / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D018692:Antimanic Agents; D051399:Aquaporin 2; D053503:Epithelial Sodium Channels; D018020:Lithium Compounds; D008094:Lithium