Prouroguanylin overproduction and localization in the intestine of zinc-deficient rats

Identification of the upregulation of preprouroguanylin mRNA in the rat small intestine during zinc deficiency provides a potential mechanistic link between production of the intestinal hormone uroguanylin and the diarrhea that may accompany zinc deficiency. In the current study, in situ hybridization demonstrated that the number of preprouroguanylin mRNA-expressing cells was significantly higher in zinc-deficient rats than in zinc-adequate rats. Immunohistochemical studies, with a uroguanylin peptide affinity-purified antibody, demonstrated that immunoreactivity was localized to the tips of villi of the duodenum and jejunum in zinc-adequate rats. However, positive cells were scattered throughout the villus of zinc-deficient rats. A subset of cells, perhaps enterochromaffin cells, exhibited the predominant staining, whereas no specific staining was found in goblet cells or lymphocytes of the lamina propria. Western blotting demonstrated that the expression of prouroguanylin in both duodenum and jejunum was elevated by dietary zinc depletion. These results show that dietary zinc deficiency upregulates prouroguanylin in intestinal cells, which is consistent with a role for uroguanylin in the etiology of diarrhea observed in human zinc deficiency.