Guanylate Cyclase Activator 2A (GUCA2A)

Binding of STa to STaR induces a dramatic increase in the cGMP content of the cell; the increase, in turn, inhibits salt absorption and stimulates chloride secretion. This imbalance of ions is accompanied by a massive accumulation of water in the gut that gives rise to the diarrhea and dehydration characteristic of enterotoxin activity. The identification of a receptor for STa on intestinal brush border membranes suggested the existence of an endogenous activator.

The sequences demonstrated that guanylin is present at the C-terminal end of a larger precursor protein. Expression in mammalian cells indicated that the 94-amino acid proguanylin is inactive. The biologically active guanylin can be released by either chemical or enzymatic treatment of proguanylin.