Increased renal responsiveness to vasopressin and enhanced V2 receptor signaling in RGS2-/- mice.
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.
Zuber
Annie Mercier
AM
Département de Pharmacologie et de Toxicologie Université de Lausanne, 27 rue du Bugnon, CH-1005 Lausanne, Switzerland.
Singer
Dustin
D
Penninger
Josef M
JM
Rossier
Bernard C
BC
Firsov
Dmitri
D
D000818:Animals; D050034:Antidiuretic Agents / Q000494:pharmacology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004326:Drinking / Q000502:physiology; D019332:Endothelin-1 / Q000494:pharmacology; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D020710:RGS Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000097:blood / Q000652:urine; D013566:Sympathomimetics / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology*; D014868:Water Deprivation / Q000502:physiology
D050034:Antidiuretic Agents; D019332:Endothelin-1; D020710:RGS Proteins; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; C105345:Rgs2 protein, mouse; D013566:Sympathomimetics; D014667:Vasopressins; D010656:Phenylephrine; D012964:Sodium; D000242:Cyclic AMP