CFTR pharmacology and its role in intestinal fluid secretion.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated Cl(-) channel expressed in epithelial cells in the airways, pancreas, intestine and other fluid-transporting tissues. Cystic fibrosis is caused by mutations in the CFTR, resulting in impaired Cl(-) transport and plasma membrane targeting. CFTR is expressed in the lumenal membrane of enterocytes, where it functions as the principal pathway for secretion of Cl(-) and fluid in enterotoxin-induced secretory diarrheas such as cholera. Small-molecule CFTR inhibitors reduce enterotoxin-induced intestinal fluid secretion in animal models. CFTR inhibition might also reduce intestinal fluid losses in cholera and possibly in other infectious and non-infectious diarrheas.
Thiagarajah
Jay R
JR
Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0521, USA.
Verkman
A S
AS
D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology / Q000627:therapeutic use; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000235:genetics / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D003967:Diarrhea / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology; D020895:Enterocytes / Q000378:metabolism; D004768:Enterotoxins / Q000378:metabolism; D007419:Intestinal Secretions / Q000502:physiology*
D000930:Antidiarrheals; D002712:Chlorides; D004768:Enterotoxins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator