Uroguanylin is expressed by enterochromaffin cells in the rat gastrointestinal tract

Background & Aims: Guanylin and uroguanylin are recently discovered intestinal peptides. identifying the type of cell that synthesizes and secretes each peptide is an important step toward defining their physiological functions. However, the site of uroguanylin expression has not been identified, and the site of guanylin expression remains controversial (some studies implicate goblet cells, whereas others implicate enterochromaffin cells). The aim of the present study was to identify cellular sites of uroguanylin expression in the rat gastrointestinal tract and resolve the guanylin localization controversy. Methods: Polyclonal antibodies against two independent regions of the uroguanylin prohormone were raised and used to evaluate prouroguanylin expression by Western blotting and immunohistochemistry. In parallel, uroguanylin mRNA was localized by in situ hybridization. Results: Uroguanylin propeptide expression is high in proximal small intestine, low in stomach and distal small intestine, and almost undetectable in large intestine. Uroguanylin-expressing eel Is are identified as a subpopulation of enterochromaffin cells. Conclusions: Previous results showing guanylin expression in enterochromaffin cells appear to be a consequence of antibody cross-reactivity for epitopes conserved between proguanylin and prouroguanylin. Expression of uroguanylin in enterochromaffin cells is consistent with the hypothesis that uroguanylin is secreted both apically (into the lumen) and basolaterally (into the circulation).