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.