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Angiotensin II Stimulates Renin Synthesis and Secretion in Mouse Collecting Duct M‐1 cells via a PKC alpha‐mediated cAMP Stimulation Mechanism
Author(s) -
LIU LIU,
Lara Lucienne S.,
Gonzalez Alexis A,
Bourgeois Camille RT,
Seth Dale M.,
Prieto Minolfa C.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1165.16
Subject(s) - forskolin , protein kinase c , endocrinology , medicine , renin–angiotensin system , calphostin c , creb , angiotensin ii , stimulation , intracellular , chemistry , activator (genetics) , protein kinase a , secretion , biology , signal transduction , kinase , receptor , gene , transcription factor , biochemistry , blood pressure
To test the hypothesis that Ang II stimulates renin synthesis and secretion in collecting duct (CD) cells via activation of PKC and subsequent stimulation of cAMP/PKA/CREB pathway, we treated mouse cortical CD (M‐1) cells with Ang II (10 −7 M). Ang II treatment for 6‐h increased intracellular renin gene expression and renin content in culture media (Ang II: 31±4 vs. 19±4 ng Ang I/hr/ml; p<0.05). Likewise, this treatment increased intracellular cAMP levels by 1 min (148±32 pmol/mg protein) which reached a peak at 30 min (290±27 vs. 44±0 pmol/mg protein; p<0.05). The adenlyate cyclase activator, forskolin and the analogue of cAMP, dibutyryl‐cAMP both significantly increased renin gene expression. These responses were followed by increases in pCREB levels and prevented by PKA inhibition with H89 or PKI. PKC inhibition either with calphostin C or a PKCα dominant negative prevented the augmentation of intracellular levels of cAMP, pCREB and renin mRNA in Ang II‐treated M‐1 cells. Ang II stimulates renin synthesis and secretion in M‐1 cells via PKCα‐mediated cAMP accumulation and PKA/CREB activation. By this mechanism distal tubular renin may contribute to local Ang II generation, thus to activation of sodium reabsorption.