Definition

An agonist of intestinal guanylate cyclase type C (GC-C) which is almost structurally identical to human uroguanylin, with laxative and anti-nociceptive activities. Upon oral administration, plecanatide binds to and activates GC-C receptors located on endothelial cells on the luminal surface of the intestinal epithelium. This increases the concentration of intracellular cyclic guanosine monophosphate (cGMP). cGMP activates the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel and stimulates the secretion of chloride and bicarbonate into the intestinal lumen. This also promotes sodium excretion into the lumen and osmosis. The increased intestinal fluid secretion accelerates gastrointestinal transit of intestinal contents, improves bowel movement, softens stool, and relieves constipation. In addition, plecanatide exerts its anti-nociceptive effects by increasing the concentration of extracellular cGMP which inhibits the activity of pain-sensitive nerves, decreases muscle contractions and may relieve intestinal pain.