Corin Deficiency Diminishes Intestinal Sodium Excretion in Mice

Area of Science:

• Physiology
• Endocrinology
• Gastroenterology

Background:

• Sodium homeostasis is vital, with kidney and intestine playing key roles in sodium excretion.
• Hormonal regulation of intestinal sodium excretion is poorly understood, unlike renal mechanisms.
• Atrial natriuretic peptide (ANP) is crucial for renal sodium excretion, activated by the protease corin.

Purpose of the Study:

• To investigate the expression and function of corin, ANP, and natriuretic peptide receptor A (Npra) in the mouse intestine.
• To elucidate the role of intestinal corin in regulating fecal sodium and chloride excretion.
• To determine the relationship between intestinal corin, cardiac corin, and aldosterone in sodium balance.

Main Methods:

• Examined corin, ANP, and Npra expression in mouse intestinal tissues using immunohistochemistry.
• Utilized wild-type (WT), global Corin knockout (KO), cardiac-specific Corin KO, and kidney-specific Corin KO mice.
• Measured fecal sodium (Na+) and chloride (Cl-) excretion in these mouse models, with and without aldosterone treatment.

Main Results:

• Corin and ANP were co-localized in intestinal enteroendocrine cells; Npra was found on luminal epithelial cells.
• Corin KO mice exhibited reduced fecal Na+ and Cl- excretion, a phenotype not observed in cardiac-specific Corin KO mice.
• Kidney-specific Corin KO mice showed increased fecal Na+ and Cl- excretion, suggesting an intestinal compensatory response.
• Aldosterone treatment abolished fecal Na+ and Cl- excretion differences between WT, Corin KO, and kidney-specific Corin KO mice.

Conclusions:

• Intestinal corin promotes fecal sodium excretion via a paracrine mechanism, independent of cardiac corin.
• Intestinal corin activity appears to antagonize aldosterone's action on fecal sodium excretion.
• These findings reveal a novel hormonal pathway for intestinal sodium excretion, contributing to overall sodium homeostasis.