Goreisan Promotes Diuresis by Regulating the Abundance of Aquaporin 2 Phosphorylated at Serine 269 Through Calcium-sensing Receptor Activation

Overview

Journal Sci Rep

Specialty Science

Date 2024 Nov 28

PMID 39609591

Authors

Keisuke Ogura

Naoki Fujitsuka

Miwa Nahata

Yohei Tokita

Affiliations

Soon will be listed here.

Abstract

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 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.

References

Ma T, Song Y, Yang B, Gillespie A, Carlson E, Epstein C . Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels. Proc Natl Acad Sci U S A. 2000; 97(8):4386-91. PMC: 18251. DOI: 10.1073/pnas.080499597. View

Ranieri M, Tamma G, Di Mise A, Russo A, Centrone M, Svelto M . Negative feedback from CaSR signaling to aquaporin-2 sensitizes vasopressin to extracellular Ca2. J Cell Sci. 2015; 128(13):2350-60. DOI: 10.1242/jcs.168096. View

Conigrave A, Mun H, Lok H . Aromatic L-amino acids activate the calcium-sensing receptor. J Nutr. 2007; 137(6 Suppl 1):1524S-1527S. DOI: 10.1093/jn/137.6.1524S. View

Zhang J, Hou A, Dong J, Zheng S, Yu H, Wang X . Screening out key compounds of Glechomae Herba for antiurolithic activity and quality control based on spectrum-effect relationships coupled with UPLC-QDA. Biomed Pharmacother. 2022; 149:112829. DOI: 10.1016/j.biopha.2022.112829. View

Kakeshita K, Imamura T, Onoda H, Kinugawa K . Impact of Goreisan upon aquaporin-2-incorporated aquaresis system in patients with congestive heart failure. CEN Case Rep. 2022; 12(1):73-77. PMC: 9892389. DOI: 10.1007/s13730-022-00723-0. View

Ranieri M, Zahedi K, Tamma G, Centrone M, Di Mise A, Soleimani M . CaSR signaling down-regulates AQP2 expression via a novel microRNA pathway in pendrin and NaCl cotransporter knockout mice. FASEB J. 2017; 32(4):2148-2159. DOI: 10.1096/fj.201700412RR. View

Rice W, Li W, Mamuya F, McKee M, Paunescu T, Lu H . Polarized Trafficking of AQP2 Revealed in Three Dimensional Epithelial Culture. PLoS One. 2015; 10(7):e0131719. PMC: 4493001. DOI: 10.1371/journal.pone.0131719. View

Loonen A, Knoers N, van Os C, Deen P . Aquaporin 2 mutations in nephrogenic diabetes insipidus. Semin Nephrol. 2008; 28(3):252-65. DOI: 10.1016/j.semnephrol.2008.03.006. View

Xie L, Hoffert J, Chou C, Yu M, Pisitkun T, Knepper M . Quantitative analysis of aquaporin-2 phosphorylation. Am J Physiol Renal Physiol. 2010; 298(4):F1018-23. PMC: 2853310. DOI: 10.1152/ajprenal.00580.2009. View

10.

Olesen E, Fenton R . Aquaporin 2 regulation: implications for water balance and polycystic kidney diseases. Nat Rev Nephrol. 2021; 17(11):765-781. DOI: 10.1038/s41581-021-00447-x. View

11.

Ranieri M, Di Mise A, Centrone M, DAgostino M, Tingskov S, Venneri M . Olive Leaf Extract (OLE) impaired vasopressin-induced aquaporin-2 trafficking through the activation of the calcium-sensing receptor. Sci Rep. 2021; 11(1):4537. PMC: 7907100. DOI: 10.1038/s41598-021-83850-5. View

12.

Suenaga A, Seto Y, Funamoto M, Imanishi M, Tsuchiya K, Ikeda Y . TJ-17 (Goreisan) mitigates renal fibrosis in a mouse model of folic acid-induced chronic kidney disease. J Pharmacol Sci. 2023; 153(1):31-37. DOI: 10.1016/j.jphs.2023.07.001. View

13.

Lee Y, Lee S, Cui X, Yoon J, Oh H, Kim Y . Quantitative evaluation of Oryeongsan and its action on water regulation in renal inner medullary collecting duct cells. J Ethnopharmacol. 2016; 185:310-8. DOI: 10.1016/j.jep.2016.03.030. View

14.

Cheng P, Meng K, Shi X, Jiao M, Han Y, Li X . Solid-phase extraction with the functionalization of calcium-sensing receptors onto magnetic microspheres as an affinity probe can capture ligands selectively from herbal extract. Mikrochim Acta. 2023; 191(1):34. DOI: 10.1007/s00604-023-06092-4. View

15.

Athwal B, Berkley K, Hussain I, Brennan A, Craggs M, Sakakibara R . Brain responses to changes in bladder volume and urge to void in healthy men. Brain. 2001; 124(Pt 2):369-77. DOI: 10.1093/brain/124.2.369. View

16.

Yaku H, Kato T, Morimoto T, Kaneda K, Nishikawa R, Kitai T . Rationale and study design of the GOREISAN for heart failure (GOREISAN-HF) trial: A randomized clinical trial. Am Heart J. 2023; 260:18-25. DOI: 10.1016/j.ahj.2023.02.013. View

17.

Moeller H, Knepper M, Fenton R . Serine 269 phosphorylated aquaporin-2 is targeted to the apical membrane of collecting duct principal cells. Kidney Int. 2008; 75(3):295-303. PMC: 3502047. DOI: 10.1038/ki.2008.505. View

18.

Valenti G, Laera A, Pace G, Aceto G, Lospalluti M, Penza R . Urinary aquaporin 2 and calciuria correlate with the severity of enuresis in children. J Am Soc Nephrol. 2000; 11(10):1873-1881. DOI: 10.1681/ASN.V11101873. View

19.

Kawakami Z, Matsubara Y, Ogura K, Imamura S, Iizuka S, Zhang N . Effect of Goreisan, a Traditional Japanese Medicine, on Rat Hindlimb Lymphedema. Biol Pharm Bull. 2024; 47(6):1179-1188. DOI: 10.1248/bpb.b23-00829. View

20.

Knepper M, Wade J, Terris J, Ecelbarger C, Marples D, Mandon B . Renal aquaporins. Kidney Int. 1996; 49(6):1712-7. DOI: 10.1038/ki.1996.253. View