Figure 4: GC-C-dependent signaling pathway of guanylin peptides in the intestine. Guanylin (GN), uroguanylin (UGN), and heat-stable enterotoxin of E. coli (STa) activate GC-C which increases intracellular concentration of cGMP which in the enterocytes causes the following: inhibits the Na+/H+ exchanger type 2 (NHE2) and activates protein kinase G type II (PKG II), activates protein kinase A (PKA) directly or indirectly by inhibition of phosphodiesterase III (PDE III) followed by increase in intracellular cAMP concentration. PKA and PKG II activate Cl- and secretion via activation of cystic fibrosis transmembrane regulator (CFTR) followed by an activation of the member of Slc26 family which exchanges bicarbonate for chloride.