title: Vasopressin/V2 receptor stimulates renin synthesis in the collecting duct.
abstract: 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.
authors.affiliation: Instituto de Química, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile; alexis.gonzalez@pucv.cl.
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Gonzalez
authors.affiliation: Instituto de Química, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile;
authors.forename: Flavia
authors.initials: F
authors.lastname: Cifuentes-Araneda
authors.affiliation: Instituto de Química, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile;
authors.forename: Cristobal
authors.initials: C
authors.lastname: Ibaceta-Gonzalez
authors.affiliation: Instituto de Química, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile;
authors.forename: Alex
authors.initials: A
authors.lastname: Gonzalez-Vergara
authors.affiliation: Instituto de Química, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile;
authors.forename: Leonardo
authors.initials: L
authors.lastname: Zamora
authors.affiliation: Instituto de Química, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile;
authors.forename: Ricardo
authors.initials: R
authors.lastname: Henriquez
authors.affiliation: Department of Physiology Tulane University, School of Medicine, New Orleans, Louisiana; and.
authors.forename: Carla B
authors.initials: CB
authors.lastname: Rosales
authors.affiliation: Department of Physiology Tulane University, School of Medicine, New Orleans, Louisiana; and Hypertension and Renal Center of Excellence, Tulane University, School of Medicine, New Orleans, Louisiana.
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
authors.affiliation: Department of Physiology Tulane University, School of Medicine, New Orleans, Louisiana; and Hypertension and Renal Center of Excellence, Tulane University, School of Medicine, New Orleans, Louisiana.
authors.forename: Minolfa C
authors.initials: MC
authors.lastname: Prieto
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000819:agonists*; D012083:Renin / Q000096:biosynthesis*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D044140:Receptor, Angiotensin, Type 1; D017483:Receptors, Vasopressin; D013449:Sulfonamides; D017868:Cyclic AMP-Dependent Protein Kinases; D012083:Renin; D003894:Deamino Arginine Vasopressin; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: PKA/CREB; collecting duct; distal tubular renin; intrarenal renin-angiotensin system; prorenin; water deprivation