Guanylin
Overview
Guanylin is a 15-amino acid endogenous peptide hormone that activates guanylate cyclase-C (GC-C) receptors on intestinal epithelial cells. Upon binding, it stimulates intracellular cyclic GMP production, which regulates chloride and bicarbonate secretion into the intestinal lumen and promotes fluid secretion. This mechanism enhances intestinal motility and fluid balance. Guanylin functions as a paracrine regulator of intestinal homeostasis and salt-water equilibrium.
Key Research Findings
Guanylin itself has been characterized primarily in preclinical studies elucidating its role in intestinal fluid regulation and epithelial cell function. Synthetic analogs of guanylin, such as linaclotide and plecanatide, have been developed and approved for clinical use in chronic constipation and irritable bowel syndrome with constipation. Native guanylin remains a research tool rather than a therapeutic agent.
Endogenous peptide
Research Phase
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Lanreotide (Somatuline Depot)
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Pasireotide (Signifor)
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Plecanatide (Trulance)
FDA ApprovedA synthetic 16-amino acid peptide structurally related to uroguanylin, an endogenous intestinal peptide that regulates fluid and electrolyte homeostasis in the GI tract. Plecanatide activates guanylate cyclase-C (GC-C) receptors on intestinal epithelial cells in a pH-dependent manner, preferentially in the proximal small intestine where pH is slightly acidic. GC-C activation increases intracellular and extracellular cGMP, stimulating chloride and bicarbonate secretion while reducing visceral pain signaling.