Open AccessIncreased Renal Responsiveness to Vasopressin and Enhanced V2 Receptor Signaling in RGS2 −/− Mice
Author(s) -
Annie Mercier Zuber,
Dustin Singer,
Josef Penninger,
Bernard C. Rossier,
Dmitri Firsov
Publication year - 2007
Publication title -
journal of the american society of nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.451
H-Index - 279
eISSN - 1533-3450
pISSN - 1046-6673
DOI - 10.1681/asn.2007010032
Subject(s) - rgs2 , vasopressin , nephron , aquaporin 2 , medicine , endocrinology , vasopressin receptor , kidney , receptor , arginine vasopressin receptor 2 , biology , regulator of g protein signaling , antidiuretic , signal transduction , chemistry , g protein , microbiology and biotechnology , water channel , gtpase activating protein , mechanical engineering , engineering , antagonist , inlet
The antidiuretic effect of vasopressin is mediated by V2 receptors (V2R) that are located in kidney connecting tubules and collecting ducts. This study provides evidence that V2R signaling is negatively regulated by regulator of G protein signaling 2 (RGS2), a member of the family of RGS proteins. This study demonstrates that (1) RGS2 expression in the kidney is restricted to the vasopressin-sensitive part of the nephron (thick ascending limb, connecting tubule, and collecting duct); (2) expression of RGS2 is rapidly upregulated by vasopressin; (3) the vasopressin-dependent accumulation of cAMP, the principal messenger of V2R signaling, is significantly higher in collecting ducts that are microdissected from the RGS2(-/-) mice compared with their wild-type littermates; and (4) analysis of urine output of mice that were exposed to water restriction followed by acute water loading revealed that RGS2(-/-) mice exhibit an increased renal responsiveness to vasopressin. It is proposed that RGS2 is involved in negative feedback regulation of V2R signaling.