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Author Notes:

Address for reprint requests and other correspondence: Y. Wang, Emory Univ. School of Medicine, Renal Division, 1639 Pierce Dr., WMRB, Rm. 3304, Atlanta, GA 30322 (e-mail: ywang68@emory.edu).

Subject:

Research Funding:

This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants R01-DK41707, R01-DK89828, and R21-DK91147 and by American Heart Association fellowship award 0000013450.

Keywords:

  • vasopressin
  • phorbol ester
  • urine concentration
  • PKA

Role of protein kinase C-α in hypertonicity-stimulated urea permeability in mouse inner medullary collecting ducts

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Journal Title:

American Journal of Physiology - Renal Physiology

Volume:

Volume 304, Number 2

Publisher:

, Pages F233-F238

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The kidney's ability to concentrate urine is vitally important to our quality of life. In the hypertonic environment of the kidney, urea transporters must be regulated to optimize function. We previously showed that hypertonicity increases urea permeability and that the protein kinase C (PKC) blockers chelerythrine and rottlerin decreased hypertonicity-stimulated urea permeability in rat inner medullary collecting ducts (IMCDs). Because PKCα knockout (PKCα−/−) mice have a urine-concentrating defect, we tested the effect of hypertonicity on urea permeability in isolated perfused mouse IMCDs. Increasing the osmolality of perfusate and bath from 290 to 690 mosmol/kgH2O did not change urea permeability in PKCα−/− mice but significantly increased urea permeability in wild-type mice. To determine whether the response to protein kinase A was also missing in IMCDs of PKCα−/− mice, tubules were treated with vasopressin and subsequently with the PKC stimulator phorbol dibutyrate (PDBu). Vasopressin stimulated urea permeability in PKCα−/− mice. Like vasopressin, forskolin stimulated urea permeability in PKCα−/− mice. We previously showed that, in rats, vasopressin and PDBu have additive stimulatory effects on urea permeability. In contrast, in PKCα−/− mice, PDBu did not further increase vasopressin-stimulated urea permeability. Western blot analysis showed that expression of the UT-A1 urea transporter in IMCDs was increased in response to vasopressin in wild-type mice as well as PKCα−/− mice. Hypertonicity increased UT-A1 phosphorylation in wild-type mice but not in PKCα−/− mice. We conclude that PKCα mediates hypertonicity-stimulated urea transport but is not necessary for vasopressin stimulation of urea permeability in mouse IMCDs.

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© 2013 the American Physiological Society

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