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The multiple roles of guanylate cyclase C, a heat stable enterotoxin receptor

Steinbrecher, Kris A.

Current Opinion in Gastroenterology: January 2014 - Volume 30 - Issue 1 - p 1–6
doi: 10.1097/MOG.0000000000000020
GASTROINTESTINAL INFECTIONS: Edited by Mitchell B. Cohen
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Purpose of review 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.

Recent findings 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.

Summary 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.

Department of Pediatrics, University of Cincinnati College of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA

Correspondence to Kris A. Steinbrecher, PhD, Cincinnati Children's Hospital Medical Center, Division of Gastroenterology, Hepatology and Nutrition, MLC 2010, 3333 Burnet Ave, Cincinnati, Ohio 45220, USA. Tel: +1 513 636 4415; fax: +1 513 636 5581; e-mail: kris.steinbrecher@cchmc.org

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins