[12] The second is the ACTGC motif (residues Ala11 to Cys15) which is the region responsible for its binding to the receptor, guanylate cyclase-C.[16] Plecanatide works as a laxative by drawing water in to the gastrointestinal tract thereby softening stool and encouraging its natural passage.

Similar to its endogenous counterpart, plecanatide activates guanylate cyclase-C on endothelial cells within the gastrointestinal tract.

[17][18] CFTR is an anion channel and upon activation it will secrete negatively charged ions, particularly chloride (Cl−) and bicarbonate (HCO3−) in to the GI tract lumen.

[19][20] This disruption to the electrochemical gradient is in part rectified by the passive secretion of positively charged sodium ions in to the lumen and water follows by osmosis.

[21] As plecanatide acts on receptors present on the apical side of endothelial cells lining the gastrointestinal tract it is able to impart its effect without ever entering circulation.

[13] As with most orally ingested peptides, plecanatide is degraded by intestinal enzymes, and so very little of the active drug enters systemic circulation.