Uroguanylin is a 16-amino-acid intestinal peptide hormone that activates guanylate cyclase C (GC-C) receptors on intestinal epithelial cells. It regulates fluid and electrolyte transport, intestinal barrier function, and has emerging roles in satiety signaling and colorectal cancer prevention. The FDA-approved drug linaclotide (Linzess) is a synthetic GC-C agonist based on the same signaling pathway. Uroguanylin is being studied as a more physiological approach to GC-C activation.
Category: GI / Metabolic. Evidence rating: D (animal/preclinical only).
Clinical status: Preclinical as a therapeutic. GC-C agonist drugs (linaclotide, plecanatide) are FDA-approved for IBS-C and chronic constipation.
Uroguanylin binds to GC-C receptors on the luminal surface of intestinal epithelial cells, stimulating intracellular cGMP production. Elevated cGMP activates CFTR chloride channels, increasing intestinal fluid secretion and accelerating transit. cGMP also strengthens tight junctions, reducing…
Safety considerations: Linaclotide and plecanatide (related GC-C agonists) have established safety profiles from Phase 3 trials and post-marketing surveillance; Primary side effect of GC-C activation is diarrhea (dose-dependent); Uroguanylin itself has not been tested in human clinical trials as a standalone therapy.
Reviewed by the PeptideAtlas Editorial Team.
| Molecular weight | ~1667 g/mol |
|---|---|
| Production method | synthetic |
| Anti-doping status | not-listed |
| US regulatory status | Uroguanylin itself is not FDA-approved. Related GC-C agonists linaclotide (Linzess) and plecanatide (Trulance) are FDA-approved for IBS-C and CIC. |
No. Linaclotide is a synthetic 14-amino-acid peptide that mimics uroguanylin's activation of GC-C receptors but has a different amino acid sequence and is more resistant to degradation. Uroguanylin is the endogenous hormone.
Preclinical mouse data suggests uroguanylin may act as a postprandial satiety signal. However, this has not been confirmed in humans, and no clinical trials are investigating uroguanylin for weight management.
Preclinical evidence is intriguing — loss of uroguanylin expression is one of the earliest events in colorectal carcinogenesis, and restoring GC-C signaling reduces tumor formation in mouse models. Clinical trials of oral uroguanylin for cancer prevention are in early planning stages.