Guanylin

GI / Fluid Secretion

Also known as: Guanylin Peptide, GUCA2A, Uroguanylin

Guanylin FamilyResearch phase: Endogenous peptide (well characterized)Regulatory: Endogenous peptide. Plecanatide is a synthetic uroguanylin analog FDA-approved for IBS-C. Linaclotide is a GC-C agonist approved for IBS-C.

Mechanism

Guanylin (and its relative uroguanylin) are small peptides made by intestinal cells that regulate fluid secretion into the gut. They activate the same receptor (GC-C) that bacterial heat-stable enterotoxins hijack to cause traveler's diarrhea. This natural mechanism inspired the development of linaclotide and plecanatide — FDA-approved drugs for IBS-C and chronic constipation.

Technical detail

Guanylin is a 15-amino-acid endogenous peptide (with two disulfide bonds) that activates guanylate cyclase C (GC-C) on intestinal epithelial cells. GC-C activation generates intracellular cGMP, which activates PKG II, phosphorylating CFTR chloride channels to drive Cl- and HCO3- secretion into the intestinal lumen, followed by paracellular Na+ and water movement. cGMP also inhibits NHE3, reducing Na+ absorption. Uroguanylin is the more potent renal isoform. The GC-C pathway is the physiological target mimicked by bacterial STa enterotoxins and by FDA-approved drugs linaclotide and plecanatide.

Build a personalized protocol with Guanylin →