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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/F518    most recent 00349.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fröhlich, O. Articles by Sands, J. M. Search for Related Content PubMed PubMed Citation Articles by Fröhlich, O. Articles by Sands, J. M.

Stimulation of UT-A1-mediated transepithelial urea flux in MDCK cells by lithium

Otto Fröhlich,¹ Deepak Aggarwal,² Janet D. Klein,² Kimilia J. Kent,² Yuan Yang,¹ Robert B. Gunn,^1, and Jeff M. Sands^1,2

¹Department of Physiology, Emory University and ²Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia

Submitted 26 July 2007 ; accepted in final form 30 December 2007

Trans-epithelial tracer urea flux across Madin-Darby canine kidney (MDCK) cells permanently expressing the urea transporter UT-A1 is stimulated by agents that activate the cAMP signaling pathway, such as vasopressin or forskolin, thus mimicking the activation of urea permeability in the inner medullary collecting duct in the presence of vasopressin. Here, we report that UT-A1-mediated urea flux is also activated two-to-threefold over background by exposing the cells to media containing LiCl. This is in contrast to reports on cortical and medullary collecting duct tubules where acute and chronic exposure to lithium (Li) suppresses the osmotic water permeability, which is also regulated by cAMP levels. The Li concentration dependence of urea flux activation was linear up to 150 mM Li. Li activated only from the basolateral side where its effect was inhibited by amiloride, presumably because Li entered the cells through a basolateral Na-H exchanger. Li and IBMX, which also weakly activated urea flux, greatly augmented each others' stimulatory effect on urea flux. However, cellular cAMP levels did not rise commensurately with urea fluxes, and even though Li augments the activation by forskolin, it greatly inhibits the forskolin-induced formation of cAMP. These results suggest that the effect of Li in this MDCK model of renal cells does not involve cAMP or at least utilizes an additional signaling pathway independent of cAMP.

cyclic AMP; Madin-Darby canine kidney cells

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