Guanylin

Guanylin is a peptide hormone secreted primarily by cells of the small intestine and colon. It plays a crucial role in regulating fluid and electrolyte balance in the intestines, particularly sodium and chloride transport.

Guanylin acts as an agonist of the guanylate cyclase-C (GC-C) receptor, which is located on the apical surface of intestinal epithelial cells. Upon binding to GC-C, guanylin stimulates the production of cyclic GMP (cGMP), a second messenger. This increase in cGMP activates protein kinase II (PKG II), leading to the phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Phosphorylation of CFTR promotes the secretion of chloride ions (Cl-) into the intestinal lumen. The increased chloride concentration then draws sodium ions (Na+) and water into the lumen, thus increasing intestinal fluid volume and promoting defecation.

In addition to its role in fluid and electrolyte regulation, guanylin may also play a role in regulating cell proliferation and differentiation in the intestinal epithelium.

Dysregulation of guanylin signaling has been implicated in various gastrointestinal disorders, including inflammatory bowel disease (IBD) and diarrhea-predominant irritable bowel syndrome (IBS-D). Synthetic guanylin analogs, such as linaclotide, are used clinically to treat chronic constipation and IBS-D by stimulating GC-C and increasing intestinal fluid secretion.

Furthermore, research suggests that guanylin may possess anti-cancer properties, potentially inhibiting the growth and metastasis of colorectal cancer cells. Studies are ongoing to explore its therapeutic potential in this area.