The diuretic effect of Goreisan involves the modulation of aquaporin 2 localization via the calcium-sensing receptor

Abstract

Aquaporin 2 (AQP2) contributes to water reabsorption and primitive urine concentration by migrating to the luminal surface of the collecting ducts in an anti-diuretic hormone-stimulated manner, and the signaling pathway involved in AQP2 localization is a target for diuretics. This study investigated whether AQP2 is involved in the diuretic effect and mechanisms of Goreisan (GRS), a traditional Japanese Kampo medicine used to treat symptoms such as edema in patients with decreased urination. GRS exerted diuretic effects on desmopressin (dDAVP)-induced decreases in urine output and inhibited phosphorylation of AQP2 at Ser269 in the renal tissues of mice. Furthermore, GRS inhibited the migration of phosphorylated AQP2 to the luminal side following forskolin (FSK) stimulation using a 3D culture model of the kidney collecting duct cell line mIMCD-3. GRS induced a transient increase in the intracellular calcium concentration via the calcium-sensing receptor (CaSR) and suppressed the FSK-stimulated increase in cAMP production. These results suggest that GRS regulates urine volume by modulating the localization of AQP2 via CaSR.