Goreisan promotes diuresis by regulating the abundance of aquaporin 2 phosphorylated at serine 269 through calcium-sensing receptor activation.

Autor: Ogura K; TSUMURA Kampo Research Laboratories, Research & Development Division, TSUMURA & CO., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan. ogura_keisuke@mail.tsumura.co.jp., Fujitsuka N; TSUMURA Kampo Research Laboratories, Research & Development Division, TSUMURA & CO., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan., Nahata M; TSUMURA Kampo Research Laboratories, Research & Development Division, TSUMURA & CO., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan., Tokita Y; TSUMURA Kampo Research Laboratories, Research & Development Division, TSUMURA & CO., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Nov 28; Vol. 14 (1), pp. 29650. Date of Electronic Publication: 2024 Nov 28.
DOI: 10.1038/s41598-024-81324-y
Abstrakt: Aquaporin 2 (AQP2) contributes to water reabsorption and 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 subcellular localization is a target for arginine vasopressin receptor antagonists (aquaretics). This study investigated the involvement of AQP2 in the diuretic effect and mechanisms of Goreisan (GRS), a traditional Japanese Kampo medicine used to treat conditions such as edema in patients with decreased urination. GRS exerted diuretic effects on desmopressin (DDAVP)-induced decreases in urine output and the level of AQP2 phosphorylated at Serine269 (pSer269-AQP2) in the renal tissues of mice. Furthermore, GRS inhibited the accumulation of pSer269-AQP2 to the luminal side following forskolin stimulation using a 3D culture model of the kidney collecting duct cell line mIMCD-3. GRS induced a transient increase in the intracellular Ca 2+ concentration via the calcium-sensing receptor (CaSR) and suppressed the forskolin-stimulated increase in cAMP production. These results suggest that GRS regulates urine volume by modulating the subcellular localization of AQP2 via CaSR.
Competing Interests: Declarations. Competing interests: All authors are employed by Tsumura & Co. This study received funding from Tsumura & Co. The funder was involved in the following aspects of the study: study design, data collection and analysis, publication decision, and manuscript preparation. The authors declare no other competing interests. Ethics approval: All animal experiments were approved by the Laboratory Animal Committee of Tsumura & Co. (approval nos. 23 − 013, 23–024) and performed in accordance with guidelines for the conduct of animal experiments from the Ministry of Health, Labour and Welfare of Japan. This study is reported in accordance with ARRIVE guidelines.
(© 2024. The Author(s).)
Databáze: MEDLINE
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