title: Bradykinin/B2receptor activation regulates renin in M-1 cells via protein kinase C and nitric oxide.
abstract: In the collecting duct (CD), the interactions of renin angiotensin system (RAS) and kallikrein-kinin system (KKS) modulate Na+reabsorption, volume homeostasis, and blood pressure. In this study, we used a mouse kidney cortical CD cell line (M-1 cells) to test the hypothesis that in the CD, the activation of bradykinin B2receptor (B2R) increases renin synthesis and release. Physiological concentrations of bradykinin (BK) treatment of M-1 cells increased renin mRNA and prorenin and renin protein contents in a dose-dependent manner and increased threefold renin content in the cell culture media. These effects were mediated by protein kinase C (PKC) independently of protein kinase A (PKA) because B2R antagonism with Icatibant and PKC inhibition with calphostin C, prevented these responses, but PKA inhibition with H89 did not modify the effects elicited by the B2R activation. BK-dependent stimulation of renin gene expression in CD cells also involved nitric oxide (NO) pathway because increased cGMP levels and inhibition of NO synthase with L-NAME prevented it. Complementary renin immunohistochemical studies performed in kidneys from mice with conventional B2R knockout and conditional B2R knockout in the CD, showed marked decreased renin immunoreactivity in CD, regardless of the renin presence in juxtaglomerular cells in the knockout mice. These results indicate that the activation of B2R increases renin synthesis and release by the CD cells through PKC stimulation and NO release, which support further the interactions between the RAS and KKS.
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.|Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana.|Tulane Hypertension and Renal Center of Excellence, Tulane University, New Orleans, Louisiana.
authors.forename: Lucienne S
authors.initials: LS
authors.lastname: Lara
authors.affiliation: Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Camille R T
authors.initials: CR
authors.lastname: Bourgeois
authors.affiliation: Tulane Hypertension and Renal Center of Excellence, Tulane University, New Orleans, Louisiana.|Department of Pediatrics, Section of Pediatric Nephrology, Tulane University Health Sciences Center, New Orleans, Louisiana.
authors.forename: Samir S
authors.initials: SS
authors.lastname: El-Dahr
authors.affiliation: Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana mprieto@tulane.edu.|Tulane Hypertension and Renal Center of Excellence, Tulane University, New Orleans, Louisiana.
authors.forename: Minolfa C
authors.initials: MC
authors.lastname: Prieto
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D065094:Bradykinin B2 Receptor Antagonists / Q000494:pharmacology; D002460:Cell Line; D007546:Isoquinolines / Q000494:pharmacology; D007672:Kidney Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D012083:Renin / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; D007546:Isoquinolines; D009281:Naphthalenes; D047428:Protein Kinase Inhibitors; D043782:Receptor, Bradykinin B2; D013449:Sulfonamides; D009569:Nitric Oxide; C065679:icatibant; D011493:Protein Kinase C; D012083:Renin; C058819:calphostin C; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester
keywords: cGMP; distal tubular renin; gene expression; prorenin; protein kinase A