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

Curr Opin Gastroenterol. 2014 Jan;30(1):1-6. doi: 10.1097/MOG.0000000000000020.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adhesins, Bacterial / physiology
  • Homeostasis / physiology
  • Humans
  • Inflammatory Bowel Diseases / enzymology*
  • Intestinal Absorption / physiology
  • Intestines / microbiology
  • Irritable Bowel Syndrome / drug therapy
  • Irritable Bowel Syndrome / enzymology*
  • Receptors, Atrial Natriuretic Factor / agonists
  • Receptors, Atrial Natriuretic Factor / physiology*
  • Signal Transduction / physiology
  • Water-Electrolyte Balance / physiology

Substances

  • Adhesins, Bacterial
  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor C