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Pharmacology and clinical potential of guanylyl cyclase C agonists in the treatment of ulcerative colitis
Authors Pitari GM
Received 31 January 2013
Accepted for publication 7 March 2013
Published 19 April 2013 Volume 2013:7 Pages 351—360
DOI https://doi.org/10.2147/DDDT.S32252
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Giovanni M Pitari
Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA
Abstract: Agonists of the transmembrane intestinal receptor guanylyl cyclase C (GCC) have recently attracted interest as promising human therapeutics. Peptide ligands that can specifically induce GCC signaling in the intestine include endogenous hormones guanylin and uroguanylin, diarrheagenic bacterial enterotoxins (ST), and synthetic drugs linaclotide, plecanatide, and SP-333. These agonists bind to GCC at intestinal epithelial surfaces and activate the receptor’s intracellular catalytic domain, an event initiating discrete biological responses upon conversion of guanosine-5'-triphosphate to cyclic guanosine monophosphate. A principal action of GCC agonists in the colon is the promotion of mucosal homeostasis and its dependent barrier function. Herein, GCC agonists are being developed as new medications to treat inflammatory bowel diseases, pathological conditions characterized by mucosal barrier hyperpermeability, abnormal immune reactions, and chronic local inflammation. This review will present important concepts underlying the pharmacology and therapeutic utility of GCC agonists for patients with ulcerative colitis, one of the most prevalent inflammatory bowel disease disorders.
Keywords: inflammatory bowel disease, GCC agonists, cyclic GMP
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