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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Renal+Physiol
2015 ; 309
(10
): F880-8
Nephropedia Template TP
gab.com Text
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English Wikipedia
PKC-?-dependent augmentation of cAMP and CREB phosphorylation mediates the
angiotensin II stimulation of renin in the collecting duct
#MMPMID26268270
Gonzalez AA
; Liu L
; Lara LS
; Bourgeois CR
; Ibaceta-Gonzalez C
; Salinas-Parra N
; Gogulamudi VR
; Seth DM
; Prieto MC
Am J Physiol Renal Physiol
2015[Nov]; 309
(10
): F880-8
PMID26268270
show ga
In contrast to the negative feedback of angiotensin II (ANG II) on
juxtaglomerular renin, ANG II stimulates renin in the principal cells of the
collecting duct (CD) in rats and mice via ANG II type 1 (AT1R) receptor,
independently of blood pressure. In vitro data indicate that CD renin is
augmented by AT1R activation through protein kinase C (PKC), but the exact
mechanisms are unknown. We hypothesize that ANG II stimulates CD renin synthesis
through AT1R via PKC and the subsequent activation of cAMP/PKA/CREB pathway. In
M-1 cells, ANG II increased cAMP, renin mRNA (3.5-fold), prorenin, and renin
proteins, as well as renin activity in culture media (2-fold). These effects were
prevented by PKC inhibition with calphostin C, PKC-? dominant negative, and by
PKA inhibition. Forskolin-induced increases in cAMP and renin expression were
prevented by calphostin C. PKC inhibition and Ca2+ depletion impaired ANG
II-mediated CREB phosphorylation and upregulation of renin. Adenylate cyclase 6
(AC) siRNA remarkably attenuated the ANG II-dependent upregulation of renin mRNA.
Physiological activation of AC with vasopressin increased renin expression in M-1
cells. The results suggest that the ANG II-dependent upregulation of renin in the
CD depends on PKC-?, which allows the augmentation of cAMP production and
activation of PKA/CREB pathway via AC6. This study defines the intracellular
signaling pathway involved in the ANG II-mediated stimulation of renin in the CD.
This is a novel mechanism responsible for the regulation of local
renin-angiotensin system in the distal nephron.