scholarly journals Role of protein kinase C in renal vasoconstriction caused by angiotensin II

1990 ◽  
Vol 259 (3) ◽  
pp. C421-C426 ◽  
Author(s):  
H. Scholz ◽  
A. Kurtz
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Rat Kidney ◽  
Channel Blockers ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Protein Kinase C Inhibitors ◽  
Kinase C ◽  
Renal Vascular

In this study we have examined the subcellar pathways along which angiotensin II (ANG II) causes renal vasoconstriction. Using the isolated perfused rat kidney model, we found that renal vasoconstriction produced by ANG II (100 pM) was not altered by the calmodulin antagonists calmidazolium (1 microM) and N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide (W-7, 10 microM) but was blunted by staurosporine (100 nM) and 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7, 50 microM), two structurally distinct putative protein kinase C inhibitors. The phorbol ester 4 alpha-phorbol 12,13-didecanoate (1-100 nM) did not alter renal vascular resistance, whereas phorbol 12-myristate 13-acetate (PMA, 1-100 nM) caused potent and dose-dependent vasoconstriction that was prevented by staurosporine (100 nM) and H-7 (50 microM). The vasoconstrictory effects of ANG II and PMA were attenuated by the calcium channel blockers verapamil (5 microM) and nifedipine (5 microM) and were reversibly inhibited when cobaltous chloride (2 mM) was added to the perfusate. Taken together, our findings support the concept that the renal vasoconstrictory effect of ANG II is essentially mediated by protein kinase C activation, which either requires or enhances the entrance of extracellular calcium.

scholarly journals Rate of calcium entry determines the rapid changes in protein kinase C activity in angiotensin II-stimulated adrenal glomerulosa cells

1994 ◽  
Vol 297 (3) ◽  
pp. 523-528 ◽  
Author(s):  
I Kojima ◽  
N Kawamura ◽  
H Shibata
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Specific Substrate ◽  
Ang Ii ◽  
Kinase C ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Peptide Phosphorylation

The present study was conducted to monitor precisely the activity of protein kinase C (PKC) in adrenal glomerulosa cells stimulated by angiotensin II (ANG II). PKC activity in cells was monitored by measuring phosphorylation of a synthetic KRTLRR peptide, a specific substrate for PKC, immediately after the permeabilization of the cells with digitonin [Heasley and Johnson J. Biol. Chem. (1989) 264, 8646-8652]. Addition of 1 nM ANG II induced a gradual increase in KRTLRR peptide phosphorylation, which reached a peak at 30 min, and phosphorylation was sustained thereafter. When the action of ANG II was terminated by adding [Sar1,Ala8]ANG II, a competitive antagonist, both Ca2+ entry and KRTLRR phosphorylation ceased rapidly, whereas diacylglyercol (DAG) content was not changed significantly within 10 min. Similarly, when blockade of Ca2+ entry was achieved by decreasing extracellular Ca2+ to 1 microM or by adding 1 microM nitrendipine, KRTLRR peptide phosphorylation was decreased within 5 min. In addition, restoration of Ca2+ entry was accompanied by an immediate increase in KRTLRR peptide phosphorylation. Under the same condition, DAG content did not change significantly. We then examined the role of the PKC pathway in ANG II-induced aldosterone production. Ro 31-8220 inhibited ANG II-induced KRTLRR phosphorylation without affecting the activity of calmodulin-dependent protein kinase II. In the presence of Ro 31-8220, ANG II-mediated aldosterone production was decreased to approx. 50%. Likewise, intracellular administration of PKC19-36, a sequence corresponding to residues 19-36 of the regulatory domain of PKC known to inhibit PKC activity, attenuated ANG II-mediated activation of PKC and aldosterone output. These results indicate a critical role of Ca2+ entry in the regulation of PKC activity by ANG II.

Effects of chloride channel blockers on rat renal vascular responses to angiotensin II and norepinephrine

2004 ◽  
Vol 286 (2) ◽  
pp. F323-F330 ◽  
Author(s):  
Joen Steendahl ◽  
Niels-Henrik Holstein-Rathlou ◽  
Charlotte Mehlin Sorensen ◽  
Max Salomonsson
Keyword(s):  
Angiotensin Ii ◽  
Niflumic Acid ◽  
Channel Blockers ◽  
Ang Ii ◽  
Renal Vasculature ◽  
Renal Vasoconstriction ◽  
Electromagnetic Flowmetry ◽  
Control Response ◽  
Renal Vascular

The aim of the present study was to investigate the role of Ca2+-activated Cl- channels in the renal vasoconstriction elicited by angiotensin II (ANG II) and norepinephrine (NE). Renal blood flow (RBF) was measured in vivo using electromagnetic flowmetry. Ratiometric photometry of fura 2 fluorescence was used to estimate intracellular free Ca2+ concentration ([Ca2+]i) in isolated preglomerular vessels from rat kidneys. Renal arterial injection of ANG II (2-4 ng) and NE (20-40 ng) produced a transient decrease in RBF. Administration of ANG II (10-7 M) and NE (5 × 10-6 M) to the isolated preglomerular vessels caused a prompt increase in [Ca2+]i. Renal preinfusion of DIDS (0.6 and 1.25 μmol/min) attenuated the ANG II-induced vasoconstriction to ∼35% of the control response, whereas the effects of NE were unaltered. Niflumic acid (0.14 and 0.28 μmol/min) and 2-[(2-cyclopentenyl-6,7-dichloro-2,3-dihydro-2-methyl-1-oxo-1 H-inden-5-yl)oxy]acetic acid (IAA-94; 0.045 and 0.09 μmol/min) did not affect the vasoconstrictive responses of these compounds. Pretreatment with niflumic acid (50 μM) or IAA-94 (30 μM) for 2 min decreased baseline [Ca2+]i but did not change the magnitude of the [Ca2+]i response to ANG II and NE in the isolated vessels. The present results do not support the hypothesis that Ca2+-activated Cl- channels play a crucial role in the hemodynamic effects of ANG II and NE in rat renal vasculature.

Regulation of vascular angiotensin II receptors by EGF

1997 ◽  
Vol 273 (4) ◽  
pp. C1241-C1249 ◽  
Author(s):  
Michael E. Ullian ◽  
John R. Raymond ◽  
Mark C. Willingham ◽  
Richard V. Paul
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Protein Kinase ◽  
Pertussis Toxin ◽  
Receptor Expression ◽  
Ang Ii ◽  
Receptor Density ◽  
Kinase C ◽  
Surface Receptor

After vascular endothelial injury, angiotensin II (ANG II) plays a role in the resulting hypertrophic response, and expression of epidermal growth factor (EGF) is enhanced. Therefore, we tested the possibility that EGF regulates vascular ANG II action and receptor expression. Incubation of cultured aortic vascular smooth muscle cells (VSMC) with EGF (or basic fibroblast growth factor but not platelet-derived growth factor isoforms) resulted in concentration-dependent (1–50 ng/ml EGF), time-dependent (>8 h), and reversible decreases in ANG II surface receptor density. For example, a 50% reduction was observed after exposure to 50 ng/ml EGF for 24 h. Incubation of cultured VSMC with 50 ng/ml EGF for 24 h resulted in a 77% reduction in ANG II-stimulated inositol phosphate formation. EGF not only prevented but also reversed ANG II receptor upregulation by 100 nM corticosterone. The specific tyrosine kinase inhibitor tyrphostin A48 (50 μM) reduced EGF-stimulated thymidine incorporation and EGF-stimulated phosphorylation of mitogen-activated protein kinase but did not prevent EGF from reducing ANG II receptor density. Neither pertussis toxin (100 ng/ml) nor downregulation of protein kinase C by phorbol myristate acetate (100 nM for 24 h) prevented EGF from reducing ANG II receptor density. In summary, EGF is a potent negative regulator of vascular ANG II surface receptor density and ANG II action by mechanisms that do not appear to include tyrosine phorphorylation, pertussis toxin-sensitive G proteins, or phorbol ester-sensitive protein kinase C. The possibility that EGF shifts the cell culture phenotype to one that exhibits reduced surface ANG II density cannot be eliminated by the present studies.

Regulation of angiotensin II binding sites in neuronal cultures by protein kinase C

1990 ◽  
Vol 258 (4) ◽  
pp. C610-C617 ◽  
Author(s):  
C. J. Kalberg ◽  
C. Sumners
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Binding Sites ◽  
Phorbol Esters ◽  
Specific Binding ◽  
Neuronal Cultures ◽  
Ang Ii ◽  
Kinase C ◽  
Stimulation Of

The radioligand binding of 125I-angiotensin II (ANG II) and calcium phospholipid-dependent protein kinase C (PKC) activity were measured to study the specificity and mechanisms of PKC involvement in the regulation of ANG II-specific binding site expression in neuronal cultures prepared from the brains of 1-day-old rats. Previously, PKC-activating phorbol esters were shown to increase the specific binding of 125I-ANG II in neuronal cultures. However, phorbol esters have many biological effects, which may nonspecifically act to increase 125I-ANG II-specific binding. In the present study, mezerein and teleocidin A, two activators of PKC that are chemically unrelated to phorbol esters, increased the specific binding of 125I-ANG II in a dose- and time-dependent manner with 50% effective dose (ED50) values of 32 and 79 nM, respectively. The PKC antagonist H-7 dose dependently inhibited phorbol 12-myristate 13-acetate (TPA)-stimulated increases in 125I-ANG II binding, whereas downregulation of PKC activity by chronic phorbol ester incubations of 24 and 48 h prevented TPA-stimulated increases in 125I-ANG II-specific binding. TPA (0.8 microM), mezerein (0.76 microM), and teleocidin A (0.5 microM) all caused a rapid translocation of PKC activity from the cytosol to the particulate fraction by 15 min. Temporally, the maximal stimulation of PKC translocation by mezerein, teleocidin A, and TPA preceded their ability to stimulate maximal 125I-ANG II-specific binding. Taken together, these results suggest that PKC is directly involved in the stimulation of ANG II-specific binding site expression and that translocation of PKC is a prerequisite for the increased expression of ANG II binding sites.

scholarly journals Angiotensin II Activates Mitogen-Activated Protein Kinase Via Protein Kinase C and Ras/Raf-1 Kinase in Bovine Adrenal Glomerulosa Cells

Endocrinology ◽  
1998 ◽  
Vol 139 (4) ◽  
pp. 1801-1809 ◽  
Author(s):  
Ying Tian ◽  
Roger D. Smith ◽  
Tamas Balla ◽  
Kevin J. Catt
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Time Course ◽  
Mitogen Activated Protein Kinase ◽  
Ang Ii ◽  
Mapk Activation ◽  
Kinase C ◽  
Mitogen Activated Protein ◽  
Glomerulosa Cells

Abstract Angiotensin II (Ang II) stimulates growth and mitogenesis in bovine adrenal glomerulosa cells, but little is known about the signaling pathways that mediate these responses. An analysis of the growth-promoting pathways in cultured bovine adrenal glomerulosa cells revealed that Ang II, acting via the AT1 receptor, caused rapid but transient activation of mitogen-activated protein kinase (MAPK), with an ED50 of 10–50 pm. Although neither Ca2+ influx nor Ca2+ release from intracellular stores was sufficient to activate MAPK, Ca2+ appeared to play a permissive role in this response. A major component of Ang II-induced MAPK activation was insensitive to pertussis toxin (PTX), although a minor PTX-sensitive component could not be excluded. Ang II also induced the rapid activation of ras and raf-1 kinase with time-courses that correlated with that of MAPK. Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate was sufficient to activate both MAPK and raf-1 kinase. However, whereas PKC depletion had no effect on Ang II-induced raf-1 kinase activation, it attenuated Ang II-induced MAPK activation. Ang II also stimulated a mobility shift of raf-1, reflecting hyperphosphorylation of the kinase. However, unlike its activation, raf-1 hyperphosphorylation was dependent on PKC and its time-course correlated not with activation, but rather with deactivation of the kinase. Taken together, these findings indicate that Ang II stimulates multiple pathways to MAPK activation via PKC and ras/raf-1 kinase in bovine adrenal glomerulosa cells.

Angiotensin-mediated phosphatidylcholine hydrolysis and protein kinase C activation in mesangial cells

1993 ◽  
Vol 265 (4) ◽  
pp. C1100-C1108 ◽  
Author(s):  
R. L. Barnett ◽  
L. Ruffini ◽  
L. Ramsammy ◽  
R. Pasmantier ◽  
M. M. Friedlaender ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Phospholipase D ◽  
Mesangial Cells ◽  
Ang Ii ◽  
Kinase C ◽  
Pi Hydrolysis ◽  
Pkc Activation ◽  
Protein Kinase C Activation

Angiotensin II (ANG II) in mesangial cells (MC) promotes phosphatidylinositol (PI) hydrolysis resulting in diacylglycerol (DAG)-mediated increases in protein kinase C (PKC) activity. The paucity of MC inositol lipid prompted us to consider whether phosphatidylcholine (PC) could sustain DAG formation. ANG II released choline and increased phosphatidylethanol (PEt) via PC-phospholipase D (PC-PLD). ANG II also stimulated phosphorylcholine consequent to PC-phospholipase C (PC-PLC) activation. ANG II-mediated PC hydrolysis augmented DAG for 30 min. PC breakdown was influenced by extracellular Ca2+, because Ni2+ partially inhibited ANG II-induced PEt and obliterated agonist-mediated DAG formation. The consequence of Ca2+ modulation of PC metabolism was investigated by measuring PKC activity. Ni2+ had no effect on early (PI-associated) activation by ANG II at 90 s but obviated translocation from cytosol to the membrane at 10 min. The pathway responsible for PC-associated DAG was studied in PKC downregulated cells. Whereas downregulation prevented PLD-mediated PEt elevation, ANG II-stimulated DAG formation in myristate-labeled cells was unaltered, indicating PC-PLC activation. In summary, ANG II stimulates PC-PLD and PC-PLC in MC. PC-PLD is tightly regulated by PKC, whereas PC-PLC is stringently controlled by extracellular Ca2+. ANG II mediated PC breakdown principally via PC-PLC provides a mechanism for maintaining elevated DAG levels and PKC activation.

Regulation of aldosterone secretion by avian adrenocortical cells

1988 ◽  
Vol 118 (3) ◽  
pp. 447-453 ◽  
Author(s):  
J. Rosenberg ◽  
M. Pines ◽  
S. Hurwitz
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Inositol Phosphate ◽  
Ionophore A23187 ◽  
Channel Blockers ◽  
Aldosterone Secretion ◽  
Adrenocortical Cells ◽  
Adrenal Cells ◽  
Kinase C

ABSTRACT Dispersed chick adrenocortical cells were incubated with mammalian and avian angiotensin-II, Ca2+, K+, verapamil, nifedipine, Ca2+ ionophore (A23187), protein kinase-C activator (phorbol 12-myristate 13-acetate; TPA), atrial natriuretic peptide (ANP), sodium nitroprusside (SNP) and ACTH. Secretion of aldosterone and corticosterone, and accumulation of cyclic nucleotides were assessed. Secretion of aldosterone was not affected by angiotensin-II, Ca2+ channel blockers, Ca2+ ionophore or TPA. ANP stimulated production of cyclic GMP (cGMP), and inhibited aldosterone secretion with a similar dose–response relationship. SNP also stimulated cGMP production and inhibited the ACTH-stimulated aldosterone secretion. The results indicate that ANP is an inhibitor of aldosterone secretion in birds and suggest that this inhibition is mediated by cGMP. In contrast to mammalian glomerulosa cells, angiotensin-II and the calcium-inositol phosphate-protein kinase C pathway appear not to be involved in the regulation of aldosterone secretion by avian adrenal cells. J. Endocr. (1988) 118, 447–453

Protein kinase Cɛ contributes to regulation of the sarcolemmal Na+-K+ pump

2001 ◽  
Vol 281 (3) ◽  
pp. C1059-C1063 ◽  
Author(s):  
Kerrie A. Buhagiar ◽  
Peter S. Hansen ◽  
Nerida L. Bewick ◽  
Helge H. Rasmussen
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Enzyme Inhibitor ◽  
Pump Current ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Kinase C

A reduction in angiotensin II (ANG II) in vivo by treatment of rabbits with the angiotensin-converting enzyme inhibitor, captopril, increases Na+-K+ pump current ( I p) of cardiac myocytes. This increase is abolished by exposure of myocytes to ANG II in vitro. Because ANG II induces translocation of the ɛ-isoform of protein kinase C (PKCɛ), we examined whether this isozyme regulates the pump. We treated rabbits with captopril, isolated myocytes, and measured I p of myocytes voltage clamped with wide-tipped patch pipettes. I p of myocytes from captopril-treated rabbits was larger than I p of myocytes from controls. ANG II superfusion of myocytes from captopril-treated rabbits decreased I p to levels similar to controls. Inclusion of PKCɛ-specific blocking peptide in pipette solutions used to perfuse the intracellular compartment abolished the effect of ANG II. Inclusion of ψɛRACK, a PKCɛ-specific activating peptide, in pipette solutions had an effect on I p that was similar to that of ANG II. There was no additive effect of ANG II and ψɛRACK. We conclude that PKCɛ regulates the sarcolemmal Na+-K+ pump.

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