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Department of Pharmacology and Experimental Therapeutics Faculty Papers
Antineoplastic activity; binding site; carboxy terminal sequence; cell differentiation; cell migration; cell proliferation; colon mucosa; colon resection; constipation; disulfide bond; drug potency; drug structure; drug targeting; Escherichia coli; human; Klebsiella; protein cleavage; review; signal transduction; tight junction; ulcerative colitis; Yersinia enterocolitica
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Pharmacology And Clinical Potential Of Guanylyl Cyclase C Agonists In The Treatment Of Ulcerative Colitis., Giovanni M Pitari
Pharmacology And Clinical Potential Of Guanylyl Cyclase C Agonists In The Treatment Of Ulcerative Colitis., Giovanni M Pitari
Department of Pharmacology and Experimental Therapeutics Faculty Papers
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 …