Vasopressin/V2 receptor stimulates renin synthesis in the collecting duct

Am J Physiol Renal Physiol. 2016 Feb 15;310(4):F284-93. doi: 10.1152/ajprenal.00360.2015. Epub 2015 Nov 25.


Renin is synthesized in the principal cells of the collecting duct (CD), and its production is increased via cAMP in angiotensin (ANG) II-dependent hypertension, despite suppression of juxtaglomerular (JG) renin. Vasopressin, one of the effector hormones of the renin-angiotensin system (RAS) via the type 2-receptor (V2R), activates the cAMP/PKA/cAMP response element-binding protein (CREB) pathway and aquaporin-2 expression in principal cells of the CD. Accordingly, we hypothesized that activation of V2R increases renin synthesis via PKA/CREB, independently of ANG II type 1 (AT1) receptor activation in CD cells. Desmopressin (DDAVP; 10(-6) M), a selective V2R agonist, increased renin mRNA (∼3-fold), prorenin (∼1.5-fold), and renin (∼2-fold) in cell lysates and cell culture media in the M-1 CD cell line. Cotreatment with DDAVP+H89 (PKA inhibitor) or CREB short hairpin (sh) RNA prevented this response. H89 also blunted DDAVP-induced CREB phosphorylation and nuclear localization. In 48-h water-deprived (WD) mice, prorenin-renin protein levels were increased in the renal inner medulla (∼1.4- and 1.8-fold). In WD mice treated with an ACE inhibitor plus AT1 receptor blockade, renin mRNA and prorenin protein levels were still higher than controls, while renin protein content was not changed. In M-1 cells, ANG II or DDAVP increased prorenin-renin protein levels; however, there were no further increases by combined treatment. These results indicate that in the CD the activation of the V2R stimulates renin synthesis via the PKA/CREB pathway independently of RAS, suggesting a critical role for vasopressin in the regulation of renin in the CD.

Keywords: PKA/CREB; collecting duct; distal tubular renin; intrarenal renin-angiotensin system; prorenin; water deprivation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Cell Line
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Deamino Arginine Vasopressin / pharmacology
  • Gene Knockdown Techniques
  • Isoquinolines / pharmacology
  • Kidney Medulla / drug effects
  • Kidney Medulla / metabolism
  • Kidney Tubules, Collecting / drug effects*
  • Kidney Tubules, Collecting / metabolism*
  • Mice
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology
  • RNA, Small Interfering / biosynthesis
  • RNA, Small Interfering / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptors, Vasopressin / agonists*
  • Renin / biosynthesis*
  • Renin-Angiotensin System / drug effects
  • Sulfonamides / pharmacology


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Isoquinolines
  • Protein Kinase Inhibitors
  • RNA, Small Interfering
  • Receptor, Angiotensin, Type 1
  • Receptors, Vasopressin
  • Sulfonamides
  • Cyclic AMP-Dependent Protein Kinases
  • Renin
  • Deamino Arginine Vasopressin
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide