Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders

Gut. 2018 Aug;67(8):1543-1552. doi: 10.1136/gutjnl-2018-316029. Epub 2018 Mar 21.


Functional gastrointestinal disorders (FGIDs) and IBDs are two of the most prevalent disorders of the GI tract and consume a significant proportion of healthcare resources. Recent studies have shown that membrane-bound guanylate cyclase-C (GC-C) receptors lining the GI tract may serve as novel therapeutic targets in the treatment of FGIDs and IBDs. GC-C receptor activation by its endogenous paracrine hormones uroguanylin and guanylin, and the resulting intracellular production of its downstream effector cyclic GMP, occurs in a pH-dependent manner and modulates key physiological functions. These include fluid and electrolyte homeostasis, maintenance of the intestinal barrier, anti-inflammatory activity and regulation of epithelial regeneration. Studies of the GC-C paracrine signalling axis have revealed the therapeutic potential of these receptors in treating GI disorders, including chronic idiopathic constipation and irritable bowel syndrome-constipation. This review focuses on the evolving understanding of GC-C function in health and disease, and strategies for translating these principles into new treatments for FGIDs and IBDs.

Keywords: chronic idiopathic constipation; guanylate cyclase C; irritable bowel syndrome-constipation; linaclotide; plecanatide; uroguanylin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Gastrointestinal Diseases / diagnosis
  • Gastrointestinal Diseases / etiology*
  • Gastrointestinal Diseases / therapy*
  • Humans
  • Receptors, Guanylate Cyclase-Coupled / physiology*


  • Receptors, Guanylate Cyclase-Coupled