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