title: Stimulation of UT-A1-mediated transepithelial urea flux in MDCK cells by lithium.
abstract: 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.
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA 30322, USA. otto.froehlich@emory.edu
authors.forename: Otto
authors.initials: O
authors.lastname: Fröhlich
authors.forename: Deepak
authors.initials: D
authors.lastname: Aggarwal
authors.forename: Janet D
authors.initials: JD
authors.lastname: Klein
authors.forename: Kimilia J
authors.initials: KJ
authors.lastname: Kent
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gunn
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Sands
mesh_terms: D000818:Animals; D050034:Antidiuretic Agents / Q000494:pharmacology; D018692:Antimanic Agents / Q000009:adverse effects*; D001127:Arginine Vasopressin / Q000494:pharmacology; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004285:Dogs; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D018021:Lithium Chloride / Q000009:adverse effects*; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D014508:Urea / Q000378:metabolism*; D000096982:Urea Transporters
chemical_list: D050034:Antidiuretic Agents; D018692:Antimanic Agents; D001127:Arginine Vasopressin; D005576:Colforsin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D018021:Lithium Chloride; D026901:Membrane Transport Proteins; D017923:Sodium-Hydrogen Exchangers; D014508:Urea; D000096982:Urea Transporters