Expression of gastrin in the thin descending limb of Henle's loop in the mouse kidney: a molecular, localization, and functional study

Abstract

Gastrin is secreted mainly by G‐cells in the stomach and released into the circulation. It is taken up by renal tubules where it acts on cholecystokinin B receptors (CCKBR) to decrease sodium reabsorption. However, it is unknown whether or not gastrin can also be produced by the kidney and participate in the control of sodium homeostasis and blood pressure.We used real‐time RT‐PCR to determine the expression of gastrin mRNA in different areas of the mouse kidney and found the gastrin transcript in both medulla and papilla, indicating that gastrin may be synthesized in the kidney. Gastrin immunoreactivity was detected in the thin descending limb of Henle's loop (TDLHL), which was confirmed by colocalization with aquaporin 1, a marker of TDLHL. Expression of gastrin protein was also found in mouse kidney homogenates. In contrast, real‐time RT‐PCR, western blotting, and immunostaining revealed no expression of gastrin in the kidney of gastrin knock‐out (Gast −/−) mice. In addition, Gast−/− mice have higher blood pressure and lower sodium excretion than Gast+/+ mice.These results show for the first time that gastrin is expressed in the TDLHL of the mouse kidney. Furthermore, renal gastrin might contribute to increase sodium excretion and maintain normal blood pressure.