title: ENaC inhibitors and airway re-hydration in cystic fibrosis: state of the art.
abstract: Cystic fibrosis (CF) is a hereditary disease caused by mutations in the gene encoding the chloride channel "cystic fibrosis transmembrane conductance regulator" (CFTR). The lack of functional CFTR in CF airways leads to impaired ion and fluid homeostasis of the fluid layer which lines the airway surfaces (ASL). The ASL is important for proper ciliary beat and clearance of mucus from the airways. According to the "low volume hypothesis", CF airway epithelia hyperabsorb sodium via the epithelial sodium channel (ENaC). Although the contribution of ENaC to CF pathogenesis is still under debate, there is convincing data demonstrating that re-hydration of the ASL might improve mucociliary clearance in CF patients. ASL re-hydration might, amongst other things, be achieved by a block of airway transepithelial sodium absorption with inhibitors of ENaC. This mini-review article describes the role of ENaC in ASL fluid homeostasis and rehydration, and summarizes the current state of the art in the discovery and establishment of compounds which inhibit ENaC activity and may represent pharmacological tools for the treatment of CF.
authors.affiliation: Institute of Animal Physiology, Justus-Liebig University of Giessen, Giessen, Germany. mike.althaus@bio.uni-giessen.de
authors.forename: Mike
authors.initials: M
authors.lastname: Althaus
mesh_terms: D000584:Amiloride / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D062686:Epithelial Sodium Channel Blockers / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D053503:Epithelial Sodium Channels / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009079:Mucociliary Clearance / Q000187:drug effects; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D058913:Purinergic Agonists / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D012964:Sodium / Q000378:metabolism
chemical_list: D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D011480:Protease Inhibitors; D058913:Purinergic Agonists; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000584:Amiloride; D012964:Sodium