Metabolic fate of orally administered cGMP in rats

Background Activation of membrane guanylate cyclase type C (GC-C) on the luminal surface of the intestinal epithelium by GCC agonists results in an increase in both intracellular and extracellular levels of cyclic guanosine monophosphate (cGMP). Elevation in intracellular cGMP results in the secretion of chloride and bicarbonate anions into the intestinal lumen through the activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. Physiologically, this results in increased intestinal fluid and accelerated transit. Furthermore, an accompanying increase in the luminal and submucosal concentration of cGMP is observed as intracellular cGMP is transported out of epithelial cells. In animal models, decreased activity of pain-sensing afferent fibers is likely mediated by increased extracellular cGMP in the submucosa [1]. Compared to the pharmacological effects elicited by the increase in cGMP, less is known about the distribution and metabolic fate of this second messenger that is transported out into the luminal space.