Vasopressin Increases Plasma Membrane Accumulation of Urea Transporter UT-A1 in Rat Inner Medullary Collecting Ducts

Emory University School of Medicine, Renal Division, WMB Room 3319B, 1639 Pierce Drive NE, Atlanta, GA 30322, USA.
Journal of the American Society of Nephrology (Impact Factor: 9.34). 11/2006; 17(10):2680-6. DOI: 10.1681/ASN.2006030246
Source: PubMed


Urea transport, mediated by the urea transporter A1 (UT-A1) and/or UT-A3, is important for the production of concentrated urine. Vasopressin rapidly increases urea transport in rat terminal inner medullary collecting ducts (IMCD). A previous study showed that one mechanism for rapid regulation of urea transport is a vasopressin-induced increase in UT-A1 phosphorylation. This study tests whether vasopressin or directly activating adenylyl cyclase with forskolin also increases UT-A1 accumulation in the plasma membrane of rat IMCD. Inner medullas were harvested from rats 45 min after injection with vasopressin or vehicle. UT-A1 abundance in the plasma membrane was significantly increased in the membrane fraction after differential centrifugation and in the biotinylated protein population. Vasopressin and forskolin each increased the amount of biotinylated UT-A1 in rat IMCD suspensions that were treated ex vivo. The observed changes in the plasma membrane are specific, as the amount of biotinylated UT-A1 but not the calcium-sensing receptor was increased by forskolin. Next, whether forskolin or the V(2)-selective agonist dDAVP would increase apical membrane expression of UT-A1 in MDCK cells that were stably transfected with UT-A1 (UT-A1-MDCK cells) was tested. Forskolin and dDAVP significantly increased UT-A1 abundance in the apical membrane in UT-A1-MDCK cells. It is concluded that vasopressin and forskolin increase UT-A1 accumulation in the plasma membrane in rat IMCD and in the apical plasma membrane of UT-A1-MDCK cells. These findings suggest that vasopressin regulates urea transport by increasing UT-A1 accumulation in the plasma membrane and/or UT-A1 phosphorylation.

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Available from: Tekla D Smith, Sep 08, 2015
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    • "During the past two decades, molecular approaches have resulted in the cloning of several urea transporter cDNA isoforms derived from two gene families: urea transporter-A type and -B type (Sands, 2003). In rats and mice, Ang II and AVP regulate urea transport and accumulation through urea transporter proteins in the kidney (Kato et al., 2000; Klein et al., 2006, 2012). We previously reported that AVT stimulated urea transport and expression of urea transporter protein and mRNA in the kidney and urinary bladder of B. marinus (Konno et al., 2007). "
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    • "and stimulates phosphorylation of UT-A1 protein (Zhang et al., 2002). This causes an increase in urea transport by increasing UT-A1 abundance at the apical plasma membrane in IMCD cells (Klein et al., 2006a). This regulation of UT-A1 activity and membrane accumulation involves rapid phosphorylation of serine 486 (Klein et al., 2010). "
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