L-Cysteinyl-L-cysteinyl-L-α-glutamyl-L-tyrosyl-L-cysteinyl-L-cysteinyl-L-asparaginyl-L-prolyl-L-alanyl-L-cysteinyl-L-threonylglycyl-L-cysteinyl-L-tyrosine Cyclic (1→6),(2→10),(5→13)-Tris(disulfide)

Linaclotide is a peptide agonist of the guanylate cyclase C receptor (Ki = 16.4nM in a radioligand binding assay using mouse intestinal mucosa).1 Luminal exposure to 5ug of linaclotide stimulates fluid secretion and cGMP concentration in jejunal loops isolated from wild-type mice but not guanylate cyclase C receptor null mice. Linaclotide (100ug/kg) increases intestinal transit in wild-type mice. It also reduces the number of phosphorylated ERK-positive dorsal horn neurons in the thoracolumbar spinal cord, a marker of nociceptive signaling, following noxious colorectal distension and mechanical hypersensitivity in a mouse model of TNBS-induced colitis.2 Formulations containing linaclotide have been used for the treatment of constipation and pain associated with irritable bowel syndrome.