Renal angiotensin II receptors and protein kinase C in diabetic rats: effects of insulin and ACE inhibition

2000 ◽  
Vol 278 (4) ◽  
pp. F603-F612 ◽  
Author(s):  
Farhad Amiri ◽  
Raul Garcia
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ace Inhibition ◽  
Treated Group ◽  
Diabetic Rats ◽  
Competitive Binding ◽  
Ang Ii ◽  
Binding Studies ◽  
Kinase C ◽  
High Insulin

It has been shown that glomerular ANG II receptors are downregulated and protein kinase C (PKC) activity is enhanced in diabetes mellitus. Therefore, we investigated glomerular and preglomerular vascular ANG II receptors and PKC isoform regulation in streptozotocin (STZ)-diabetic rats treated with insulin and/or captopril. Diabetic rats were prepared by injecting STZ (60 mg/kg). Those that developed diabetes after 48 h were treated with low or high doses of insulin, or with a low dose of insulin as well as captopril, and killed 14 days later. Their glomeruli and preglomerular vessels were purified, competitive binding studies were performed by using the ANG II antagonists losartan and PD-123319, and PKC analysis was carried out by Western blotting. Competitive binding studies showed that the AT1 receptor was the only ANG II receptor detected on both glomeruli and preglomerular vessels of all groups. Preglomerular vascular AT1 receptor density (Bmax) was significantly upregulated in low insulin-treated STZ rats, whereas glomerular AT1 Bmax was downregulated. Furthermore, both the captopril- and high insulin-treated groups had less glomerulosclerosis and vascular damage than the low insulin-treated group. PKCα, PKCδ, PKCε, and PKCμ isoforms found in preglomerular vessels were upregulated by captopril and high insulin doses, respectively, whereas no such regulation occurred in glomeruli. We conclude that in STZ-diabetic rats ANG II receptors and PKC isoforms on preglomerular vessels and glomeruli are differentially regulated by treatment with insulin and/or captopril.

Diminished specific activity of cytosolic protein kinase C in sciatic nerve of streptozocin-induced diabetic rats and its correction by dietary myo-inositol

Diabetes ◽  
1991 ◽  
Vol 40 (11) ◽  
pp. 1545-1554 ◽  
Author(s):  
J. Kim ◽  
E. H. Rushovich ◽  
T. P. Thomas ◽  
T. Ueda ◽  
B. W. Agranoff ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Sciatic Nerve ◽  
Specific Activity ◽  
Diabetic Rats ◽  
Cytosolic Protein ◽  
Kinase C

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.

ANG II controls Na+-K+( NH 4 + )-2Cl−cotransport via 20-HETE and PKC in medullary thick ascending limb

1998 ◽  
Vol 274 (4) ◽  
pp. C1047-C1056 ◽  
Author(s):  
Hassane Amlal ◽  
Christian LeGoff ◽  
Catherine Vernimmen ◽  
Manoocher Soleimani ◽  
Michel Paillard ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Thick Ascending Limb ◽  
Ang Ii ◽  
Diacylglycerol Lipase ◽  
Medullary Thick Ascending Limb ◽  
Kinase C ◽  
Cell Ph ◽  
Cytochrome P 450

Cell pH was monitored in medullary thick ascending limbs to determine effects of ANG II on Na+-K+([Formula: see text])-2Cl−cotransport. ANG II at 10−16to 10−12 M inhibited 30–50% ( P < 0.005), but higher ANG II concentrations were stimulatory compared with the 10−12 M ANG II level cotransport activity; eventually, 10−6 M ANG II stimulated 34% cotransport activity ( P < 0.003). Inhibition by 10−12M ANG II was abolished by phospholipase C (PLC), diacylglycerol lipase, or cytochrome P-450-dependent monooxygenase blockade; 10−12 M ANG II had no effect additive to inhibition by 20-hydroxyeicosatetranoic acid (20-HETE). Stimulation by 10−6 M ANG II was abolished by PLC and protein kinase C (PKC) blockade and was partially suppressed when the rise in cytosolic Ca2+ was prevented. All ANG II effects were abolished by DUP-753 (losartan) but not by PD-123319. Thus ≤10−12 M ANG II inhibits via 20-HETE, whereas ≥5 × 10−11 M ANG II stimulates via PKC Na+-K+([Formula: see text])-2Cl−cotransport; all ANG II effects involve AT1 receptors and PLC activation.

ANG II-mediated inhibition of neuronal delayed rectifier K+ current: role of protein kinase C-α

2001 ◽  
Vol 281 (1) ◽  
pp. C17-C23 ◽  
Author(s):  
Sheng-Jun Pan ◽  
Mingyan Zhu ◽  
Mohan K. Raizada ◽  
Colin Sumners ◽  
Craig H. Gelband
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Esters ◽  
Delayed Rectifier ◽  
Dependent Manner ◽  
Ang Ii ◽  
Mediated Effects ◽  
Kinase C ◽  
K Current ◽  
Pkc Isozymes

It was previously determined that ANG II and phorbol esters inhibit Kv current in neurons cultured from newborn rat hypothalamus and brain stem in a protein kinase C (PKC)- and Ca2+-dependent manner. Here, we have further defined this signaling pathway by investigating the roles of “physiological” activators of PKC and different PKC isozymes. The cell-permeable PKC activators, diacylglycerol (DAG) analogs 1,2-dioctanoyl- sn-glycerol (1 μmol/l, n = 7) and 1-oleoyl-2-acetyl- sn-glycerol (1 μmol/l, n = 6), mimicked the effect of ANG II and inhibited Kv current. These effects were abolished by the PKC inhibitor chelerythrine (1 μmol/l, n = 5) or by chelation of internal Ca2+ ( n = 8). PKC antisense (AS) oligodeoxynucleotides (2 μmol/l) against Ca2+-dependent PKC isoforms were applied to the neurons to manipulate the endogenous levels of PKC. PKC-α-AS ( n = 4) treatment abolished the inhibitory effects of ANG II and 1-oleoyl-2-acetyl- sn-glycerol on Kv current, whereas PKC-β-AS ( n = 4) and PKC-γ-AS ( n = 4) did not. These results suggest that the angiotensin type 1 receptor-mediated effects of ANG II on neuronal Kv current involve activation of PKC-α.

Bidirectional modulation of parathyroid hormone-responsive adenylyl cyclase by protein kinase C

1994 ◽  
Vol 266 (6) ◽  
pp. E897-E904 ◽  
Author(s):  
A. M. Kitten ◽  
T. K. Hymer ◽  
M. S. Katz
Keyword(s):  
Protein Kinase C ◽  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Adenylyl Cyclase ◽  
Catalytic Subunit ◽  
Mrna Levels ◽  
Binding Studies ◽  
Kinase C ◽  
Bidirectional Modulation ◽  
Umr 106

The temporal pattern with which phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), modulates parathyroid hormone (PTH)-responsive adenylyl cyclase (AC) was evaluated in a clonal osteoblast-like cell line (UMR-106). Brief (< or = 1 h) exposure of UMR-106 cells to PMA enhanced PTH stimulation of AC, whereas more prolonged PMA treatment decreased the PTH response, with maximum inhibition occurring at < or = 6 h. PMA treatment also resulted in initial activation followed by downregulation of PKC. Exposure of cells to 1,2-dioctanoyl-sn-glycerol, which activated but did not downregulate PKC, resulted in bidirectional modulation of PTH-responsive AC identical to that produced by PMA. Prolonged PMA exposure decreased PTH receptor number, as determined by radioligand binding studies, and reduced PTH receptor mRNA levels, assessed by Northern blot analysis. Forskolin activation of the catalytic subunit of AC was also decreased after prolonged PMA treatment. The results suggest that activation of PKC sequentially stimulates and then inhibits PTH responsiveness. Inhibition of the PTH response occurs by PKC actions exerted on the PTH receptor and the AC catalytic subunit.

Sign in / Sign up

Export Citation Format

Share Document