title: The multiple roles of guanylate cyclase C, a heat stable enterotoxin receptor.
abstract: OBJECTIVE
  Guanylate cyclase C (GC-C) is a transmembrane receptor that is expressed primarily on intestinal epithelial cells. Activation of this receptor by its endogenous peptide ligands initiates cyclic guanosine monophosphate-dependent (cGMP) salt and water movement in the intestine. GC-C is targeted by the enterotoxigenic Escherichia coli heat-stable enterotoxin STa, which deregulates this pathway and causes secretory diarrhea. This review discusses current work on the physiological function of GC-C in the intestine.
  
  
  RESULTS
  Familial GC-C mutations demonstrate that epithelial cGMP signaling is critical to electrolyte and fluid balance in the neonatal intestine. Chronic deregulation of GC-C activity in early life increases susceptibility to a number of disorders, including obstruction and inflammatory bowel disease. Murine models indicate that GC-C regulates the composition of intestinal commensal microflora and that it suppresses bacterial infection and modulates colonic injury and inflammation. Therapeutic GC-C ligands are used to successfully treat constipation-predominant irritable bowel syndrome and recent studies show that extracellular cGMP is an important mechanism of reducing abdominal pain associated with this disorder.
  
  
  CONCLUSIONS
  Originally identified as a target of E. coli enterotoxin STa, GC-C is an important regulator of physiological salt and water homeostasis and may directly impact a wide range of intestinal disorders.
authors.affiliation: Department of Pediatrics, University of Cincinnati College of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Kris A
authors.initials: KA
authors.lastname: Steinbrecher
mesh_terms: D018829:Adhesins, Bacterial / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000201:enzymology*; D007408:Intestinal Absorption / Q000502:physiology; D007422:Intestines / Q000382:microbiology; D043183:Irritable Bowel Syndrome / Q000188:drug therapy / Q000201:enzymology*; D017461:Receptors, Atrial Natriuretic Factor / Q000819:agonists / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology
chemical_list: D018829:Adhesins, Bacterial; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C