scholarly journals Angiotensin II Stimulates Renin in Inner Medullary Collecting Duct Cells via Protein Kinase C and Independent of Epithelial Sodium Channel and Mineralocorticoid Receptor Activity

Hypertension ◽  
2011 ◽  
Vol 57 (3) ◽  
pp. 594-599 ◽  
Author(s):  
Alexis A. Gonzalez ◽  
Liu Liu ◽  
Lucienne S. Lara ◽  
Dale M. Seth ◽  
L. Gabriel Navar ◽  
...  
Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 942
Author(s):  
Yuanbin Zhang ◽  
Dongfang Liu ◽  
Fan Xue ◽  
Hongli Yu ◽  
Hao Wu ◽  
...  

This study evaluated the anti-ascites effect of total diterpenoids extracted from Euphorbiae ebracteolatae Radix (TDEE) on malignant ascitic mice and elucidated its underlying mechanism. TDEE was extracted by dichloromethane and subjected to column chromatography. The purity of six diterpenoids isolated from TDEE was determined to be 77.18% by HPLC. TDEE (3 and 0.6 g raw herbs/kg, p.o.) reduced ascites and increased urine output. Meanwhile, analysis of tumor cell viability, cycle and apoptosis indicated that TDEE had no antitumor activity. In addition, the expression levels of aquaporins (AQPs) and the membrane translocation levels of protein kinase C (PKC) α and PKCβ in kidney and cells were measured. TDEE reduced the levels of AQP1–4, and inhibited PKCβ expression in membrane fraction. Four main diterpenoids, except compound 2, reduced AQP1 level in human kidney-2 cells. Compounds 4 and 5 inhibited AQP2–4 expression in murine inner medullary collecting duct cells. The diterpenoid-induced inhibition of AQP1–4 expression was blocked by phorbol-12-myristate-13-acetate (PMA; agonist of PKC). The diterpenoids from TDEE are the main anti-ascites components. The anti-ascites effect of diterpenoids may be associated with alterations in AQPs in the kidneys to promote diuresis. The inhibition of AQP1–4 expression by TDEE is related to the inhibition of PKCβ activation.


1990 ◽  
Vol 259 (4) ◽  
pp. F666-F671 ◽  
Author(s):  
I. N. Slotki ◽  
J. H. Schwartz ◽  
E. A. Alexander

In this study we investigated the role of protein kinases in activation of the Na(+)-H+ exchanger in inner medullary collecting duct (IMCD) cells. Monolayers, 24-48 h after achieving confluence, were made quiescent by 24 h incubation in 0.1% serum before study. Changes in pHi were measured with 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Phorbol myristate acetate (PMA), a synthetic analogue of diacylglycerol (DAG), was used to stimulate protein kinase C (PKC). In nominally HCO3(-)-free media containing 110 mM Na+ and 1 mM Ca2+, PMA addition increased pHi from 7.29 +/- 0.08 to 7.54 +/- 0.07 after 20 min. The increment in pHi was completely inhibited by 1 mM amiloride or by replacement of extracellular Na+ with choline but not inhibited by 1 mM N-ethylmaleimide, an inhibitor of active proton transport. Downregulation of PKC by overnight incubation of monolayers with PMA also prevented the rise in pHi upon subsequent challenge with PMA. Another active analogue of DAG, 1,2-dioleoyl-rac-glycerol, caused an increment in pHi similar to that produced by PMA, whereas 4 alpha-phorbol, an inactive analogue, did not stimulate Na(+)-H+ exchange. Bradykinin (10(-6) M), a phospholipase C-activating hormone, also induces alkalinization of IMCD cells similar to that produced by phorbol esters. Neither vasopressin (10(-7) M), which induces cellular accumulation of adenosine 3-,5--cyclic monophosphate (cAMP) and activation of protein kinase A (PKA), nor 8-bromo-cAMP (1 mM) changed pHi. Therefore in the IMCD cell activation of PKC but not PKA stimulates a rise in pHi via the Na(+)-H+ exchanger.


2004 ◽  
Vol 287 (2) ◽  
pp. F299-F304 ◽  
Author(s):  
Lijun Yao ◽  
Dan-Yang Huang ◽  
Imke L. Pfaff ◽  
Xin Nie ◽  
Michael Leitges ◽  
...  

In mouse kidney, the conventional protein kinase C (PKC) isoenzyme α is expressed in glomeruli, the cortical collecting duct (intercalated cells only), and medullary collecting duct. To get insights on its function, PKC-α knockout (−/−) and wild-type (+/+) mice were studied. When provided free access to water, PKC-α −/− mice showed ∼50% greater urine flow rate and lower urinary osmolality in 24-h metabolic cage experiments despite a greater urinary vasopressin-to-creatinine ratio vs. PKC-α +/+ mice. Renal albumin excretion was not different. Clearance experiments under inactin/ketamine anesthesia revealed a modestly reduced glomerular filtration rate and showed a reduced absolute and fractional renal fluid reabsorption in PKC-α −/− mice. The sodium-restricting response to a low-sodium diet was unaffected in PKC-α −/− mice. Urinary osmolality was reduced to similar hypotonic levels in PKC-α −/− and +/+ mice during acute oral water loading or application of the vasopressin V2-receptor antagonist SR-121463. In comparison, the lower urinary osmolality observed in PKC-α −/− mice vs. wild-type mice under basal conditions persisted during water restriction for 36 h. In conclusion, PKC-α appears not to play a major role in renal sodium reabsorption but, consistent with its expression in the medullary collecting duct, contributes to urinary concentration in mice. Considering that PKC-βI and -βII are coexpressed with PKC-α in mouse medullary collecting duct, the present results indicate that conventional PKC isoenzymes cannot fully compensate for each other.


2000 ◽  
Vol 279 (5) ◽  
pp. F835-F840 ◽  
Author(s):  
Akihiko Kato ◽  
Janet D. Klein ◽  
Chi Zhang ◽  
Jeff M. Sands

Angiotensin II receptors are present along the rat inner medullary collecting duct (IMCD), although their physiological role is unknown. Because urea is one of the major solutes transported across the terminal IMCD, we measured angiotensin II's effect on urea permeability. In the perfused rat terminal IMCD, angiotensin II had no effect on basal urea permeability but significantly increased vasopressin-stimulated urea permeability by 55%. Angiotensin II, both without and with vasopressin, also increased the amount of 32P incorporated into urea transporter (UT)-A1 in inner medullary tissue exposed to these hormones ex vivo. Because angiotensin II activates protein kinase C, we tested the effect of staurosporine (SSP). In the absence of angiotensin II, SSP had no effect on vasopressin-stimulated urea permeability in the perfused terminal IMCD. However, SSP completely and reversibly blocked the angiotensin II-mediated increase in vasopressin-stimulated urea permeability. SSP and chelerythrine reduced the angiotensin II-stimulated 32P incorporation into UT-A1 in inner medullary tissue exposed ex vivo. We conclude that angiotensin II increases vasopressin-stimulated facilitated urea permeability and32P incorporation into the 97- and 117-kDa UT-A1 proteins via a protein kinase C-mediated signaling pathway. These data suggest that angiotensin II augments vasopressin-stimulated facilitated urea transport in the rat terminal IMCD and may play a physiological role in the urinary concentrating mechanism by augmenting the maximal response to vasopressin.


2004 ◽  
Vol 287 (2) ◽  
pp. F289-F298 ◽  
Author(s):  
Stephanie Redling ◽  
Imke L. Pfaff ◽  
Michael Leitges ◽  
Volker Vallon

Localization of protein kinase C (PKC) isoenzymes α, βI, βII, δ, and ε was studied employing Western blot analysis and immunohistochemical methods including confocal laser-scanning microscopy in the kidney of two mice strains, namely, C57BL/6 and 129/Sv, which have recently been used as genetic backgrounds for respective knockout mice. Immunoblot analysis identified immunoreactive bands for each isoenzyme in total kidney cell extracts. Isoenzyme expression sites were identical for both strains. Glomeruli expressed PKC-α, -βI, and -ε. The latter isoenzme was also detected in apical aspects of proximal convoluted but not in proximal straight tubules. In contrast to rats, neither PKC-α nor PKC-βI was detectable in the proximal tubule. Immunofluorescence was observed in luminal membranes of medullary (MTAL) and cortical thick ascending limbs for PKC-βI and in MTAL for PKC-ε. The cortical collecting duct expressed PKC-α, -βI, and -δ in intercalated cells only. In the outer medullary collecting duct, PKC-α and -βI were detectable in principal cells, whereas PKC-δ was found in intercalated cells. In the inner medullary collecting duct, PKC-α, -βI, and -βII were detected. As described for the rat, the expression of PKC-βII was otherwise restricted to cortical and medullary interstitial cells. The specificity of all labeling was confirmed in respective PKC isoenzyme knockout mice. In summary, distinct expression patterns were shown for PKC isoenzymes α, βI, βII, δ, and ε in the mouse kidney.


1995 ◽  
Vol 6 (4) ◽  
pp. 1223-1229
Author(s):  
E Schlatter ◽  
S Haxelmans ◽  
I Ankorina ◽  
R Kleta

In principal cells of rat cortical collecting ducts (CCD) cellular pH (pHi) is regulated by basolateral Na+/H+ exchange. The influence of various agonists on pHi and cellular Ca2+ activity ([Ca2+]i) in freshly isolated CCD cells was examined with BCECF and fura-2 fluorescence ratios. The recovery of pHi per minute (delta pH/min) after an acid load was 0.26 +/- 0.03 (N = 53) in control conditions and was increased by the diadenosine polyphosphates Ap4A, Ap5A, Ap6A, the phorbol ester phorbol 12-myristat 13-acetate (PMA) (each 5 mumol/L) and angiotensin II (100 nmol/L) by 0.05 +/- 0.02 (N = 10), 0.11 +/- 0.05 (N = 13), 0.09 +/- 0.02 (N = 24), 0.10 +/- 0.03 (N = 7), and 0.09 +/- 0.03 (N = 8), respectively. Vasopressin (10 nmol/L) decreased delta pH/min by 0.11 +/- 0.03 (N = 9); ATP and Ap3A (each 5 mumol/L) had no significant effect. The increase in delta pH/min with Ap6A was abolished in the presence of an inhibitor of protein kinase C, calphostin C (0.1 mumol/l, N = 8). Fura-2 fluorescence ratio was not significantly changed with angiotensin II, Ap3A, or Ap4A but increased with vasopressin, ATP, Ap5A, and Ap6A by 0.08 +/- 0.02 (N = 13), 0.04 +/- 0.02 (N = 13), 0.03 +/- 0.01 (N = 14), and 0.03 +/- 0.01 (N = 10), respectively. These data indicate that Na+/H+ exchange in rat CCD is activated by the stimulation of a Ca(2+)-independent protein kinase C and inhibited by protein kinase A.


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