000009559 001__ 9559 000009559 005__ 20240418145604.0 000009559 0247_ $$2DOI$$a10.6083/rj430538n 000009559 037__ $$aIR 000009559 245__ $$aUtilizing chemogenetic tools to study distal convoluted tubule function 000009559 260__ $$bOregon Health and Science University 000009559 269__ $$a2022-04-08 000009559 336__ $$aAbstract 000009559 520__ $$aAlthough it is the smallest segment of the nephron, the distal convoluted tubule (DCT) plays an outsized role in electrolyte homeostasis through regulation of several ions, including sodium. In the DCT, sodium balance is primarily determined by the regulation of the sodium-chloride cotransporter (NCC). When phosphorylated, NCC reabsorbs sodium away from the lumen of the nephron. Dephosphorylation of NCC inactivates this reabsorption resulting in increased sodium excretion. A similar effect is leveraged by a common class of anti-hypertensive medications called thiazides, which block NCC activity. Gaining a better understanding of the molecular mechanism by which NCC is regulated holds high clinical relevance to several diseases including hypertension, FHHt, and Gitelman syndrome. To investigate a novel mechanism that may regulate NCC activity, we implemented a cell-specific chemogenetic approach with Designer Receptors Exclusively Activated by Designer Drugs (DREADD) technology. 000009559 540__ $$fCC BY 000009559 542__ $$fIn copyright - joint owners 000009559 650__ $$aNatriuresis$$022713 000009559 650__ $$aKidney$$021185 000009559 650__ $$aHypertension$$020538 000009559 6531_ $$aDREADD 000009559 6531_ $$asodium-chloride cotransporter 000009559 6531_ $$adistal convoluted tubule 000009559 6531_ $$achemogenetics 000009559 691__ $$aSchool of Medicine$$041369 000009559 692__ $$aDivision of Nephrology and Hypertension$$041464 000009559 7001_ $$aBradford, Tanner$$uOregon Health and Science University$$041354 000009559 7001_ $$aMartz, Kevin$$uOregon Health and Science University$$041354 000009559 7001_ $$aSu, Xiao-Tong$$uOregon Health and Science University$$041354 000009559 7001_ $$aMaeoka, Yujiro$$uOregon Health and Science University$$041354 000009559 7001_ $$aSharma, Avika$$uOregon Health and Science University$$041354 000009559 7001_ $$aMcCormick, Jim$$uOregon Health and Science University$$041354 000009559 7001_ $$aEllison, David$$uOregon Health and Science University$$041354 000009559 7001_ $$aNelson, Jonathan$$uOregon Health and Science University$$041354 000009559 711__ $$aResearch Week$$uOregon Health and Science University$$d2022 000009559 8564_ $$958e719d7-8aee-467b-8c48-fd19613c7611$$s161251$$uhttps://digitalcollections.ohsu.edu/record/9559/files/Bradford_Tanner_ResearchWeek2022_DREADDAbstract_OHSU_Format.pdf 000009559 905__ $$a/rest/prod/rj/43/05/38/rj430538n 000009559 980__ $$aResearch Week