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

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.

• Authors: Kris A Steinbrecher
• Journal: Current opinion in gastroenterology (Curr Opin Gastroenterol) Vol. 30 Issue 1 Pg. 1-6 (Jan 2014) ISSN: 1531-7056 [Electronic] United States
• PMID: 24304979 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

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

Topics

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