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Collecting duct principal, but not intercalated, cell prorenin receptor regulates renal sodium and water excretion

The collecting duct is the predominant nephron site of prorenin and prorenin receptor (PRR) expression. We previously demonstrated that the collecting duct PRR regulates epithelial Na channel (ENaC) activity and water transport; however, which cell type is involved remains unclear. Herein, we examin...

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Bibliographic Details
Published in:American journal of physiology. Renal physiology 2018-09, Vol.315 (3), p.F607-F617
Main Authors: Ramkumar, Nirupama, Stuart, Deborah, Mironova, Elena, Abraham, Nikita, Gao, Yang, Wang, Shuping, Lakshmipathi, Jayalakshmi, Stockand, James D, Kohan, Donald E
Format: Article
Language:English
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Summary:The collecting duct is the predominant nephron site of prorenin and prorenin receptor (PRR) expression. We previously demonstrated that the collecting duct PRR regulates epithelial Na channel (ENaC) activity and water transport; however, which cell type is involved remains unclear. Herein, we examined the effects of principal cell (PC) or intercalated cell (IC) PRR deletion on renal Na and water handling. PC or IC PRR knockout (KO) mice were obtained by crossing floxed PRR mice with mice harboring Cre recombinase under the control of the AQP2 or B1 subunit of the H ATPase promoters, respectively. PC KO mice had reduced renal medullary ENaC-α abundance and increased urinary Na losses on a low-Na diet compared with controls. Conversely, IC KO mice had no apparent differences in Na balance or ENaC abundance compared with controls. Acute treatment with prorenin increased ENaC channel number and open probability in acutely isolated cortical collecting ducts from control and IC PRR KO, but not PC PRR KO, mice. Furthermore, compared with controls, PC KO, but not IC KO mice, had increased urine volume, reduced urine osmolality, and reduced abundance of renal medullary AQP2. Taken together, these findings indicate that PC, but not IC, PRR modulates ENaC activity, urinary Na excretion, and water transport.
ISSN:1931-857X
1522-1466
DOI:10.1152/ajprenal.00122.2018