guanylin

Guanylin is a peptide hormone of the guanylin family that regulates intestinal fluid and electrolyte balance. It is produced by the mucosal epithelium of the large intestine and secreted into the intestinal lumen. Guanylin is encoded by the GUCA2A gene, and its closely related family member uroguanylin is encoded by GUCA2B and is mainly expressed in the small intestine.

Guanylin and uroguanylin act on the guanylate cyclase-C (GC-C) receptor on the apical surface of intestinal enterocytes. Receptor activation stimulates production of cyclic GMP (cGMP), which in turn activates downstream signaling that opens the CFTR chloride channel. This increases secretion of chloride, bicarbonate, and water into the lumen, contributing to stool hydration and electrolyte balance. The signaling also influences mucosal growth and barrier function through cGMP pathways.

Physiological significance includes regulation of intestinal fluid homeostasis and possibly mucosal health. Dysregulation of guanylin signaling, including downregulation of GUCA2A observed in colorectal cancer, is an area of ongoing research. Pharmacologically, synthetic GC-C agonists that mimic guanylin signaling are used to treat certain constipation-predominant disorders by promoting intestinal secretion; examples include linaclotide and plecanatide.