title: Mechanisms Underlying Dysregulation of Electrolyte Absorption in Inflammatory Bowel Disease-Associated Diarrhea.
abstract: Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are chronic relapsing inflammatory disorders of the gastrointestinal tract. Chronic inflammation of the intestine affects the normal fluid and electrolyte absorption leading to diarrhea, the hallmark symptom of IBD. The management of IBD-associated diarrhea still remains to be a challenge, and extensive studies over the last 2 decades have focused on investigating the molecular mechanisms underlying IBD-associated diarrhea. These studies have shown that the predominant mechanism of diarrhea in IBD involves impairment of electroneutral NaCl absorption, with very little role if any played by anion secretion. The electroneutral NaCl absorption involves coupled operation of Na/H exchanger 3 (NHE3 or SLC9A3) and Cl/HCO3 exchanger DRA (Down Regulated in Adenoma, or SLC26A3). Increasing evidence now supports the critical role of a marked decrease in NHE3 and DRA function and/or expression in IBD-associated diarrhea. This review provides a detailed analysis of the current knowledge related to alterations in NHE3 and DRA function and expression in IBD including the mechanisms underlying these observations and highlights the potential of these transporters as important and novel therapeutic targets.
authors.affiliation: *Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois; and †Jesse Brown VA Medical Center, Chicago, Illinois.
authors.forename: Shubha
authors.initials: S
authors.lastname: Priyamvada
authors.forename: Rochelle
authors.initials: R
authors.lastname: Gomes
authors.forename: Ravinder K
authors.initials: RK
authors.lastname: Gill
authors.forename: Seema
authors.initials: S
authors.lastname: Saksena
authors.forename: Waddah A
authors.initials: WA
authors.lastname: Alrefai
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Dudeja
mesh_terms: D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism*; D003967:Diarrhea / Q000209:etiology / Q000503:physiopathology*; D004573:Electrolytes / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000503:physiopathology*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D000076988:Sulfate Transporters
chemical_list: D027963:Chloride-Bicarbonate Antiporters; D004573:Electrolytes; C081011:SLC26A3 protein, human; C000613385:SLC9A3 protein, human; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D000076988:Sulfate Transporters; D012965:Sodium Chloride