Background & Aims: Guanylin and uroguanylin are recently discovered in
testinal peptides. identifying the type of cell that synthesizes and s
ecretes each peptide is an important step toward defining their physio
logical functions. However, the site of uroguanylin expression has not
been identified, and the site of guanylin expression remains controve
rsial (some studies implicate goblet cells, whereas others implicate e
nterochromaffin cells). The aim of the present study was to identify c
ellular sites of uroguanylin expression in the rat gastrointestinal tr
act and resolve the guanylin localization controversy. Methods: Polycl
onal antibodies against two independent regions of the uroguanylin pro
hormone were raised and used to evaluate prouroguanylin expression by
Western blotting and immunohistochemistry. In parallel, uroguanylin mR
NA was localized by in situ hybridization. Results: Uroguanylin propep
tide expression is high in proximal small intestine, low in stomach an
d distal small intestine, and almost undetectable in large intestine.
Uroguanylin-expressing eel Is are identified as a subpopulation of ent
erochromaffin cells. Conclusions: Previous results showing guanylin ex
pression in enterochromaffin cells appear to be a consequence of antib
ody cross-reactivity for epitopes conserved between proguanylin and pr
ouroguanylin. Expression of uroguanylin in enterochromaffin cells is c
onsistent with the hypothesis that uroguanylin is secreted both apical
ly (into the lumen) and basolaterally (into the circulation).