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Vol. 15, Issue 12, 5693-5699, December 2004

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Regulation of the Vasopressin V2 Receptor by Vasopressin in Polarized Renal Collecting Duct Cells

J.H. Robben ^*, N.V.A.M. Knoers , and P.M.T. Deen ^* 

^* Department of Physiology, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands; Department of Human Genetics, University Medical Center Nijmegen, 6500 HB Nijmegen, The Netherlands

Submitted April 23, 2004; Revised September 21, 2004; Accepted September 23, 2004
Monitoring Editor: Keith Mostov

Binding of arginine-vasopressin (AVP) to its V2 receptor (V2R) in the basolateral membrane of principal cells induces Aquaporin-2–mediated water reabsorption in the kidney. To study the regulation of the V2R by dDAVP in a proper model, a polarized renal cell line stably-expressing V2R-GFP was generated. Labeled AVP-binding studies revealed an equal basolateral vs. apical membrane distribution for V2R-GFP and endogenous V2R. In these cells, GFP-V2R was expressed in its mature form and localized for 75% in the basolateral membrane and for 25% to late endosomes/lysosomes. dDAVP caused a dose- and time-dependent internalization of V2R-GFP, which was completed within 1 h with 100 nM dDAVP, was prevented by coincubation with a V2R antagonist, and which reduced its half-life from 11.5 to 2.8 h. Semiquantification of the V2R-GFP colocalization with E-cadherin (basolateral membrane), early endosomal antigen-1 (EEA-1) and lysosome-associated membrane protein-2 (LAMP-2) in time revealed that most dDAVP-bound V2R was internalized via early endosomes to late endosomes/lysosomes, where it was degraded. The dDAVP-internalized V2R did not recycle to the basolateral membrane. In conclusion, we established the itinerary of the V2R in a polarized cell model that likely resembles the in vivo V2R localization and regulation by AVP to a great extent.

Corresponding author. E-mail address: p.deen{at}ncmls.ru.nl.

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