Tissue distribution and plasma concentration of human guanylin

Guanylin, a peptide homologue of the bacterial heat-stable enterotoxins, is an endogenous activator of guanylate cyclase C (GC-C). We determined the tissue content and plasma concentration of human guanylin, and its cellular source in the intestine. Human guanylin is distributed widely from the duodenum to the rectum, the highest content being in the ileum and proximal colon. The plasma concentration of immunoreactive guanylin in the normal individuals tested was 30.3 +/- 3.7 fmol/ml (mean +/- SE) and that in patients with chronic renal failure was elevated with increasing serum creatinine concentration. Guanylin immunoreactivity was detected in the villus epithelial cells in the small intestine and these guanylin-containing cells were increased in number along the cephalocaudal axis of the gut. Guanylin was also present in Paneth cells in the small intestine and superficial epithelial cells in the large intestine. Guanylin mRNA was detected in the intestine by the reverse transcription-polymerase chain reaction. Guanylin may have paracrine action on neighboring enterocytes, activating intestinal guanylate cyclase and thereby regulating intestinal fluid as well as electrolyte transport through the second messenger, cyclic GMP.