About this item:

312 Views | 0 Downloads

Author Notes:

Correspondence: Dr. Jeff M. Sands, Emory University School of Medicine, Renal Division, 1639 Pierce Drive, NE, WMB Room 338, Atlanta, GA 30322. Phone: 404-727-2525. Fax: 404-727-3425. Email: jeff.sands@emory.edu.

There are no conflicts of interest to disclose.

Subjects:

Research Funding:

This work was supported by National Institutes of Health Grants R01-DK41707, P01-DK61521, and R01-DK62081.

Epac Regulates UT-A1 to Increase Urea Transport in Inner Medullary Collecting Ducts

Tools:

Journal Title:

Journal of the American Society of Nephrology

Volume:

Volume 20, Number 9

Publisher:

, Pages 2018-2024

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Urea plays a critical role in the concentration of urine, thereby regulating water balance. Vasopressin, acting through cAMP, stimulates urea transport across rat terminal inner medullary collecting ducts (IMCD) by increasing the phosphorylation and accumulation at the apical plasma membrane of UT-A1. In addition to acting through protein kinase A (PKA), cAMP also activates Epac (exchange protein activated by cAMP). In this study, we tested whether the regulation of urea transport and UT-A1 transporter activity involve Epac in rat IMCD. Functional analysis showed that an Epac activator significantly increased urea permeability in isolated, perfused rat terminal IMCD. Similarly, stimulating Epac by adding forskolin and an inhibitor of PKA significantly increased urea permeability. Incubation of rat IMCD suspensions with the Epac activator significantly increased UT-A1 phosphorylation and its accumulation in the plasma membrane. Furthermore, forskolin-stimulated cAMP significantly increased ERK 1/2 phosphorylation, which was not prevented by inhibiting PKA, indicating that Epac mediated this phosphorylation of ERK 1/2. Inhibition of MEK 1/2 phosphorylation decreased the forskolin-stimulated UT-A1 phosphorylation. Taken together, activation of Epac increases urea transport, accumulation of UT-A1 at the plasma membrane, and UT-A1 phosphorylation, the latter of which is mediated by the MEK–ERK pathway.

Copyright information:

© 2009 by the American Society of Nephrology

Export to EndNote