
-   GC-C receptor activation by its endogenous paracrine hormones uroguanylin (GUCA2B) and guanylin(GUCA2A), and the resulting intracellular production of its downstream effector cyclic GMP, occurs in a pH-dependent manner and modulates key physiological functions [PMID: 29563144, PMID: 27688649]. Uroguanylin activates GC-C with maximum potency in the slightly acidic (pH 5-6) environments of the duodenum and proximal jejunum, and guanylin activates GC-C in neutral to slightly basic pH environments and is principally expressed in the colorectum by goblet cells [PMID: 9122260].
-   Guanylyl cyclase C (GC-C) serves as the receptor for bacterial heat-stable enterotoxin (ST) peptides [PMID: 19960363].
-   Both linaclotide and plecanatide activate the GUCY2C receptor and stimulate fluid secretion and cGMP production [PMID: 29563144]. Linaclotide is a agonist of guanylate cyclase-C (GUCY2C or GC-C) that reduces symptoms associated with irritable bowel syndrome with constipation (IBS-C)[PMID: 23958540]. Plecanatide or dolcanatide attenuates visceral hypersensitivity via activation of guanylate cyclase-C in rat models [PMID: 29740204].
