Guanylin (GUCA2A)

Guanylin (GUCA2A) is a 15-amino acid intestinal peptide hormone secreted predominantly by goblet cells of the colon and other epithelial cells throughout the gastrointestinal tract. It acts as the endogenous ligand for guanylate cyclase C (GUCY2C), regulating fluid and electrolyte transport by increasing intracellular cyclic GMP upon receptor activation. Guanylin’s physiological roles include intestinal and renal ion homeostasis, mucosal barrier maintenance, and control of epithelial proliferation. Pathologically, loss of guanylin expression is a frequent, early event in colorectal cancer, linking its activity to tumor suppression and highlighting its value as a biomarker. Therapeutic targeting of the GC-C signaling axis via guanylin-mimetic drugs is clinically validated for bowel disorders such as constipation.

Other names

GuanylinHMW-guanylinGUCA2AGUCA2GCAP-ISTARAGuanylate cyclase activator 2AGuanylate cyclase-activating protein 1Guanylate cyclase-activating protein Iprepro-guanylin

Drugs such as linaclotide, plecanatide, and dolcanatide mimic guanylin by agonizing GC-C, triggering production of cGMP, stimulating chloride and bicarbonate secretion, and reducing fluid absorption for treatment of constipation and irritable bowel syndrome