Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders

Scott A. Waldman, Michael Camilleri

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1543-1552
Number of pages10
JournalGut
Volume67
Issue number8
DOIs
StatePublished - Aug 1 2018

Keywords

  • chronic idiopathic constipation
  • guanylate cyclase C
  • irritable bowel syndrome-constipation
  • linaclotide
  • plecanatide
  • uroguanylin

ASJC Scopus subject areas

  • Gastroenterology

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