title: Role of epithelial ion transports in inflammatory bowel disease.
abstract: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with a complex pathogenesis. Diarrhea is a highly prevalent and often debilitating symptom of IBD patients that results, at least in part, from an intestinal hydroelectrolytic imbalance. Evidence suggests that reduced electrolyte absorption is more relevant than increased secretion to this disequilibrium. This systematic review analyses and integrates the current evidence on the roles of epithelial Na(+)-K(+)-ATPase (NKA), Na(+)/H(+) exchangers (NHEs), epithelial Na(+) channels (ENaC), and K(+) channels (KC) in IBD-associated diarrhea. NKA is the key driving force of the transepithelial ionic transport and its activity is decreased in IBD. In addition, the downregulation of apical NHE and ENaC and the upregulation of apical large-conductance KC all contribute to the IBD-associated diarrhea by lowering sodium absorption and/or increasing potassium secretion.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal; and MedInUP-Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal.
authors.forename: Diogo
authors.initials: D
authors.lastname: Magalhães
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal; and MedInUP-Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal.
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Cabral
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal; and MedInUP-Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal.
authors.forename: Patrício
authors.initials: P
authors.lastname: Soares-da-Silva
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal; and MedInUP-Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal fm@med.up.pt.
authors.forename: Fernando
authors.initials: F
authors.lastname: Magro
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology*; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D065569:Gastrointestinal Absorption; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D017136:Ion Transport; D049990:Membrane Transport Modulators / Q000627:therapeutic use; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D053503:Epithelial Sodium Channels; D005765:Gastrointestinal Agents; D049990:Membrane Transport Modulators; D015221:Potassium Channels; D017923:Sodium-Hydrogen Exchangers; D000254:Sodium-Potassium-Exchanging ATPase
keywords: K+ channels; Na+-K+-ATPase; Na+/H+ exchangers; epithelial Na+ channels; inflammatory bowel disease