β-Adrenergic, Angiotensin II, and Bradykinin Receptors Enhance Neurotransmission in Human Kidney

Hypertension ◽  
1995 ◽  
Vol 26 (3) ◽  
pp. 445-451 ◽  
Author(s):  
Lars C. Rump ◽  
Christine Bohmann ◽  
Ulrike Schaible ◽  
Wolfgang Schultze-Seemann ◽  
Peter J. Schollmeyer
Keyword(s):  
Angiotensin Ii ◽  
Human Kidney ◽  
Bradykinin Receptors

Abstract 196: Involvement of Peroxynitrite Formation in Angiotensin II Induced Changes in Na+K+ATPase Activity in HK2 Cells

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Arpan K Maiti ◽  
Mohammed T Islam ◽  
Ryosuke Satou ◽  
Dewan S Majid
Keyword(s):  
Angiotensin Ii ◽  
Colorimetric Assay ◽  
Renin Angiotensin System ◽  
Human Kidney ◽  
Protective Role ◽  
Renal Tubules ◽  
Proximal Tubule Cell ◽  
Wide Range ◽  
Induced Changes ◽  
Hk2 Cells

Angiotensin II (AngII) induces both superoxide (O 2 - ) and nitric oxide (NO) generation forming peroxynitrite (ONOO - ) in biological systems. To determine the role of ONOO - in AngII induced sodium excretory responses, we examined Na + K + ATPase (NKA) activity in cultured HK2 cells (human kidney proximal tubule cell line) incubated for 30 min with a wide range (10 pM to 200 μM) of AngII concentrations (conc) in the presence or absence of a ONOO - scavenger, mercapto-ethyl-guanadine (MEG; 200μM). Post incubation HK2 cellular membrane fractions were used for measurement of NKA activity via colorimetric assay capable of detecting inorganic phosphate (Pi). Baseline value of NKA activity in these HK2 cells was measured as 10.3 ±0.7 μmoles of Pi liberated/mg protein/hr (n=12). AngII exerts dose-dependent differential effects on NKA activity. Compared to the baseline value, NKA activity was increased at lower conc (13.7±1.3% at 10 pM to 19.6±1.5% at 100nM) and decreased at higher conc (-6.0±0.8% at 1 μM to -38±2.1% at 200 μM ) without any significant effect at 500 nM conc (-1.2±0.6%) of AngII. Interestingly, MEG treatment markedly attenuated these AngII induced changes in NKA activity, both at lower conc (activity increased only to 7.8±0.67% at 10 pM and to 8.9±0.57% at 100nM; an average reduction of 33.2±2.4% in stimulatory effects) and at higher conc (activity decreased to -3.0±0.7% at 1 μM and to -20±0.57% at 200 μM; an average reduction of 54.4±4.1% in inhibitory effects). Co-incubation with O 2 - scavenger, tempol (1 mM) or NO synthase inhibitor, nitro-L-arginine methyl ester (100 μM) did not alter these AngII induced responses in HK2 cells indicating that neither O 2 - , nor NO, was directly involved in mediating these responses. AT 1 receptor (AT 1 R) blocker, losartan (10μM) treatment prevented these AngII induced changes on NKA activity confirming the involvement of AT 1 R signaling in these responses. These findings demonstrate a direct contributory role for concomitant ONOO - generation in mediating AngII induced changes in NKA activity in the proximal tubular cells. These data also suggest a reno-protective role for ONOO - in minimizing sodium retaining action of AngII by the renal tubules, particularly in the conditions associated with enhanced renin-angiotensin system.

scholarly journals Determination of an Angiotensin II-regulated Proteome in Primary Human Kidney Cells by Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC)

2013 ◽  
Vol 288 (34) ◽  
pp. 24834-24847 ◽  
Author(s):  
Ana Konvalinka ◽  
Joyce Zhou ◽  
Apostolos Dimitromanolakis ◽  
Andrei P. Drabovich ◽  
Fei Fang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Culture ◽  
Angiotensin Ii ◽  
Stable Isotope ◽  
Isotope Labeling ◽  
Human Kidney ◽  
Stable Isotope Labeling ◽  
Kidney Cells

Expression of angiotensin II type 1 receptor-interacting molecule in normal human kidney and IgA nephropathy

2010 ◽  
Vol 299 (4) ◽  
pp. F720-F731 ◽  
Author(s):  
Shin-ichiro Masuda ◽  
Kouichi Tamura ◽  
Hiromichi Wakui ◽  
Akinobu Maeda ◽  
Toru Dejima ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Iga Nephropathy ◽  
Renin Angiotensin System ◽  
Human Kidney ◽  
Receptor Signaling ◽  
Angiotensin System ◽  
Biopsy Specimens ◽  
Normal Human Kidney ◽  
Normal Human

The intrarenal renin-angiotensin system plays a crucial role in the regulation of renal circulation and sodium reabsorption through the activation of vascular, glomerular, and tubular angiotensin II type 1 (AT1) receptor signaling. We previously cloned a molecule that specifically interacted with the murine AT1 receptor to inhibit AT1 receptor signaling, which we named ATRAP (for AT1 receptor-associated protein). Since murine ATRAP was shown to be highly expressed in the kidney, in the present study we investigated expression and distribution of human ATRAP in normal kidney and renal biopsy specimens from patients with IgA nephropathy. In the normal human kidney, both ATRAP mRNA and protein were widely and abundantly distributed along the renal tubules from Bowman's capsule to the medullary collecting ducts. In all renal tubular epithelial cells, the ATRAP protein colocalized with the AT1 receptor. In renal biopsy specimens with IgA nephropathy, a significant positive correlation between ATRAP and AT1 receptor gene expression was observed. There was also a positive relationship between tubulointerstitial ATRAP expression and the estimated glomerular filtration rate in patients with IgA nephropathy. Furthermore, we examined the function of the tubular AT1 receptor using an immortalized cell line of mouse distal convoluted tubule cells (mDCT) and found that overexpression of ATRAP by adenoviral gene transfer suppressed the angiotensin II-mediated increases in transforming growth factor-β production in mDCT cells. These findings suggest that ATRAP might play a role in balancing the renal renin-angiotensin system synergistically with the AT1 receptor by counterregulatory effects in IgA nephropathy and propose an antagonistic effect of tubular ATRAP on AT1 receptor signaling.

scholarly journals Human kidney-2 cells harbor functional dopamine D1 receptors that require Giα for Gq/11α signaling

2013 ◽  
Vol 305 (4) ◽  
pp. F560-F567 ◽  
Author(s):  
Indira D. Pokkunuri ◽  
Gaurav Chugh ◽  
Mohammad Asghar
Keyword(s):  
Angiotensin Ii ◽  
Pertussis Toxin ◽  
Human Kidney ◽  
D1 Receptor ◽  
Dependent Manner ◽  
Downstream Signaling ◽  
Chelerythrine Chloride ◽  
Q Protein ◽  
Hk2 Cells ◽  
Rubidium Transport

A recent study demonstrated that the dopamine D1 receptor (D1R) is nonfunctional in human kidney cells, HK2 cells, in terms of their inability to couple to G s protein in response to the D1R agonist fenoldopam. Since D1R also couples to G q protein, we tested whether D1R is functional in HK2 cells in terms of their ability to couple to G q and produce downstream signaling. For comparison, we also studied another receptor, angiotensin II type 1 receptor (AT1R) known to couple to G q. Protein kinase C (PKC) and 86rubidium transport activities were determined as surrogate downstream signaling markers. Fenoldopam and angiotensin II increased PKC activity, which decreased in the presence of respective receptor antagonists (SCH23390 for D1R; candesartan for AT1R), PKC (chelerythrine chloride) and G i protein (pertussis toxin) inhibitors and G q/11α siRNA. Furthermore, fenoldopam and angiotensin II increased 35S-GTPγS binding, an index of receptor-G protein coupling, which decreased with pertussis toxin and in G q/11α-depleted cells. Also, fenoldopam-mediated inhibition of 86rubidium transport (an index of Na-K-ATPase activity) was attenuated with SCH23390, chelerythrine chloride, pertussis toxin, and G q/11α siRNA. Moreover, fenoldopam caused a decrease in cytosolic and increase in membranous abundance of G q/11α. The immunoprecipitated levels of G q/11α in the membranes were greater in fenoldopam-treated cells, and G iα coimmunoprecipitated with G q/11α. Our results suggest that both D1R and AT1R are functional in HK2 cells, enabling G q-mediated downstream signaling in a G i dependent manner.

scholarly journals Angiotensin II disrupts the cytoskeletal architecture of human urine-derived podocytes and results in activation of the renin-angiotensin system

2021 ◽  
Author(s):  
Lars Erichsen ◽  
Martina Bohndorf ◽  
Md. Shaifur Rahman ◽  
Wasco Wruck ◽  
James Adjaye
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Disease Modeling ◽  
Renin Angiotensin System ◽  
Human Kidney ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Renal Progenitor Cells ◽  
Potential Applications ◽  
Unique Cell

AbstractHigh blood pressure is one of the major public health problems which causes severe disorders in several tissues including the human kidney. One of the most important signaling pathways associated with the regulation of blood pressure is the renin-angiotensin system (RAS), with its main mediator angiotensin II (ANGII). Elevated levels of circulating and intracellular ANGII and aldosterone lead to pro-fibrotic, -inflammatory and -hypertrophic milieu that causes remodelling and dysfunction in cardiovascular and renal tissues. Furthermore, ANGII has been recognized as major risk factor for the induction of apoptosis in podocytes, ultimately leading to chronic kidney disease (CDK).In the past, disease modeling of kidney-associated malignancies was extremely difficult, as the derivation of kidney originated cells is very challenging. Here we describe a differentiation protocol for reproducible differentiation of SIX2-positive urine derived renal progenitor cells (UdRPCs) into mature podocytes bearing typical foot processes. The UdRPCs-derived podocytes show the ability to execute Albumin endocytosis and the activation of the renin-angiotensin system by being responsive to ANGII stimulation. Our data reveals the ANGII dependent downregulation ofNPHS1andSYNPO, resulting in the disruption of the complex podocyte cytoskeletal architecture, as shown by immunofluorescence-based detection of α–ACTININ. In the present manuscript we confirm and propose UdRPCs as a unique cell type useful for studying nephrogenesis and associated diseases. Furthermore, the responsiveness of UdRPCs-derived podocytes to ANGII implies potential applications in nephrotoxicity studies and drug screening.

Influence of norepinephrine and angiotensin II on vasomotion of renal blood supply in humans

1987 ◽  
Vol 252 (5) ◽  
pp. H941-H944 ◽  
Author(s):  
N. K. Hollenberg ◽  
M. Meyerovitz ◽  
D. P. Harrington ◽  
T. Sandor
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Renal Blood Flow ◽  
Blood Supply ◽  
Human Kidney ◽  
Oscillatory Behavior ◽  
Oscillatory Activity ◽  
Power Spectral ◽  
Insight Into

Oscillatory behavior of smooth muscle, including arterial smooth muscle, has been identified in many preparations. In this study we have extended observations on vasomotion of the renal blood supply in humans by assessing the response to norepinephrine or angiotensin II infused directly into the renal artery in doses sufficient to reduce renal blood flow by 25-33% but not influence blood pressure. In placebo-treated patients, renal blood flow and the indexes of vasomotion determined by an estimation of power spectral density of xenon transit through the human kidney did not change. Norepinephrine induced a striking increase in the amplitude but not the cycle length of oscillatory activity, whereas angiotensin (despite a somewhat larger reduction in renal blood flow) induced only a modest change in amplitude. The phasic response to norepinephrine infused continuously makes it unnecessary to invoke phasic norepinephrine release in the response to maneuvers that increase sympathetic nervous system activity. Moreover, oscillatory activity reflects phenomena that may be related to but are not dependent on changes in mean renal blood flow. The results of this study may provide insight into the pathogenesis of the increase in vasomotion evident in the renal blood supply of some patients with essential hypertension.

Abstract P171: Superoxide via Transcription Factor Sp3 Up-regulates Renal Angiotensin II Receptor Function

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Mohammad Saleem
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Human Kidney ◽  
Receptor Function ◽  
Angiotensin Ii Receptor ◽  
Percent Change ◽  
Nuclear Levels ◽  
And Function ◽  
Hk2 Cells

Oxidative stress is linked to the up-regulation of angiotensin II type 1 receptor (AT1R) function and hypertension. Here we tested the mechanism of oxidative stress-associated up-regulation of AT1 receptor function in human kidney HK2 cells. Diethyldithiocarbamate (DETC), a superoxide dismutase inhibitor, and hydrogen peroxide (H 2 O 2 ) increased DHE and DCFHDA fluorescence respectively [DHE fluorescence (Control vs DETC vs DETC + tempol vs H 2 O 2 : 0.5397 ± 0.07057, 1.463 ± 0.1671, 0.2661 ± 0.01776, 0.6406 ± 0.04821); DCFH fluorescence (Control vs H 2 O 2 vs 3-AT vs DETC: 555.9 ± 21.22, 673.5 ± 37.05, 736.1 ± 33.79, 427.7 ± 22.17)]. DETC increased nuclear levels of Sp3 protein that were attenuated with tempol (Control vs DETC, vs DETC + tempol: 0.50 ± 0.08, 1.28 ± 0.21, 0.52 ± 0.12 densities). However, H 2 O 2 had no significant effect on nuclear Sp3 (Control vs H 2 O 2, vs H 2 O 2 + tempol: Sp3, 0.50 ± 0.08, 0.68 ± 0.14, 1.04 ± 0.30 densities). In transfection studies, Sp3 plasmid increased (Control vs Sp3: 0.1165 ± 0.01, 0.3810 ± 0.03, densities) while Sp3 siRNA decreased (Control siRNA vs Sp3 siRNA: 1.11 ± 0.25, 0.64 ± 0.06, densities) the levels of AT1R protein in cell lysate. DETC increased AT1R protein expression that was attenuated by tempol, measured by immunoblotting (Control vs DETC vs DETC + tempol: 0.3535 ± 0.99, 0.9975 ± 0.19, 0.3250 ± 0.02 densities). Furthermore, DETC increased cell membrane levels of AT1R protein as measured by biotinylation and immunoblotting. This effect was attenuated by tempol. (Control vs DETC vs DETC + tempol: 100 ± 0.0, 189.8 ± 0.34.60, 102.3 ± 10.77 densities, percent change). Moreover, DETC increased PKC activity in response to angiotensin II, an indicator of AT1R function. This effect was attenuated with candesartan and tempol. (Control vs Ang II vs DETC + AngII vs DETC + Cand + AngII vs DETC + tempol: 100.0 ± 0.0, 162.0 ± 12.97, 224.9 ± 52.97, 126.0 ± 6.133, 73.32 ± 35.01 percent change) These results suggest that superoxide but not H 2 O 2 increase nuclear Sp3 protein that up-regulates renal AT1R expression and function.

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