Corin Deficiency Diminishes Intestinal Sodium Excretion in Mice

Abstract

Sodium excretion, a critical process in sodium homeostasis, occurs in many tissues, including the kidney and intestine. Unlike in the kidney, the hormonal regulation of intestinal sodium excretion remains unclear. Atrial natriuretic peptide (ANP) is a crucial hormone in renal natriuresis. Corin is a protease critical for ANP activation. Corin and ANP are expressed mainly in the heart. In this study, we investigated corin, ANP, and natriuretic peptide receptor A (Npra) expression in mouse intestines. Corin and ANP expression was co-localized in enteroendocrine cells, whereas Npra expression was on the luminal epithelial cells. In Corin knockout (KO) mice, fecal Na+ and Cl− excretion decreased compared with that in wild-type (WT) mice. Such a decrease was not found in conditional Corin KO mice lacking cardiac corin selectively. In kidney conditional Corin KO mice lacking renal corin, fecal Na+ and Cl− excretion increased, compared to that in WT mice. When WT, Corin KO, and the kidney conditional KO mice were treated with aldosterone, the differences in fecal Na+ and Cl− levels disappeared. These results suggest that intestinal corin may promote fecal sodium excretion in a paracrine mechanism independent of the cardiac corin function. The increased fecal sodium excretion in the kidney conditional Corin KO mice likely reflected an intestinal compensatory response to renal corin deficiency. Our results also suggest that intestinal corin activity may antagonize aldosterone action in the promotion of fecal sodium excretion. These findings help us understand the hormonal mechanism controlling sodium excretion the intestinal tract.