Characterization of angiotensin II receptor subtypes in human glomeruli and mesangial cells

1992 ◽  
Vol 262 (3) ◽  
pp. F432-F441 ◽  
Author(s):  
D. Chansel ◽  
S. Czekalski ◽  
P. Pham ◽  
R. Ardaillou
Keyword(s):  
Angiotensin Ii ◽  
Mesangial Cells ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Angiotensin Ii Receptor ◽  
Functional Responses ◽  
At1 Antagonists ◽  
Angiotensin Ii Receptor Subtypes ◽  
High Concentrations

This study was designed to identify the subtypes of angiotensin II (ANG II) receptors present on glomeruli and glomerular mesangial cells and establish their functional significance. Dup 753 and its metabolite EXP 3174, two nonpeptide ANG II-1 receptor (AT1) antagonists, displaced 125I-ANG II and its analogue 125I-[Sar1,Ala8]ANG II from their binding sites in rat and human glomeruli and cultured human mesangial cells, whereas CGP 42112 A and PD 123177, two ANG II-2 receptor (AT2) antagonists, exhibited little displacing activity. Dup 753 and EXP 3174 did not modify the dissociation constant (Kd) value but markedly decreased the number of sites of 125I-[Sar1,Ala8]ANG II binding. The addition of PD 123177 did not further inhibit binding when all AT1 sites were occupied by Dup 753. Binding was markedly reduced by dithiothreitol. EXP 3174 and Dup 753 inhibited the main biological functions of ANG II in mesangial cells including increases in intracellular calcium concentration, PGE2 production, and protein synthesis. PD 123177 was also active but at concentrations 1,000- to 10,000-fold greater than those of AT1 antagonists. These results indicate that 1) only AT1 receptors are present in glomeruli and glomerular mesangial cells; 2) these receptors mediate the functional responses to ANG II; 3) the nonpeptide AT1 antagonists behave as noncompetitive inhibitors; and 4) high concentrations of the nonpeptide AT2 antagonists can recognize AT1 sites.

Angiotensin II receptor subtypes determine induced NO production in rat glomerular mesangial cells

2000 ◽  
Vol 279 (6) ◽  
pp. F1092-F1100 ◽  
Author(s):  
Jörg Schwöbel ◽  
Tina Fischer ◽  
Bettina Lanz ◽  
Markus Mohaupt
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Mesangial Cells ◽  
Receptor Expression ◽  
Receptor Subtypes ◽  
No Production ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Nitrite Production ◽  
The Impact

Angiotensin II (ANG II) and nitric oxide (NO) have contrasting vascular effects, yet both sustain inflammatory responses. We investigated the impact of ANG II on lipopolysaccharide (LPS)/interferon-γ (IFN)-induced NO production in cultured rat mesangial cells (MCs). LPS/IFN-induced nitrite production, the inducible form of nitric oxide synthase (NOS-2) mRNA, and protein expression were dose dependently inhibited by ANG II on coincubation, which was abolished on ANG II type 2 (AT2) receptor blockade by PD-123319. Homology-based RT-PCR verified the presence of AT1A, AT1B, and AT2 receptors. To shift the AT receptor expression toward the type 1 receptor, two sets of experiments were performed: LPS/IFN preincubation for 24 h was followed by 8-h coincubation with ANG II; or during 24-h coincubation of LPS/IFN and ANG II, dexamethasone was added for the last 6-h period. Both led to an amplified overall expression of NOS-2 protein and NO production that was inhibitable by actinomycin D in the first setup. Induced NO production was enhanced via the AT1 receptor; however, it was diminished via the AT2 receptor. In conclusion, induced NO production is negatively controlled by the AT2, whereas AT1 receptor stimulation enhanced NO synthesis in MCs. The overall NO availability depended on the onset of the inflammatory stimuli with respect to ANG II exposure and the available AT receptors.

Angiotensin II receptor subtypes in cultured rat renal mesangial cells

1992 ◽  
Vol 263 (3) ◽  
pp. F411-F416 ◽  
Author(s):  
P. Ernsberger ◽  
J. Zhou ◽  
T. H. Damon ◽  
J. G. Douglas
Keyword(s):  
Binding Sites ◽  
Mesangial Cells ◽  
Specific Binding ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Specific Binding Sites ◽  
Angiotensin Ii Receptor Subtypes ◽  
G Protein Coupled ◽  
Two Populations

The selective angiotensin (ANG II) antagonists losartan (DuP 753) and PD 123319 have been shown to bind selectively to AT1 and AT2 subtypes, respectively. To characterize ANG II receptor subtypes in mesangial cells, washed membranes were incubated with 0.1 to 0.5 nM 125I-ANG II and increasing concentrations of competitors. The inhibition of 125I-ANG II binding by losartan and PD 123319 was biphasic, and LIGAND curve-fitting analysis revealed two populations of specific binding sites. One subpopulation comprised 86% of the total and showed high affinity for ANG II and losartan, but low affinity for the AT2 antagonists PD 123319 and CGP42112A, and thus appear identical to the recently cloned AT1 subtype. The remaining 14% of the sites showed nearly 100-fold lower affinity for losartan and 10,000-fold higher affinity for PD 123319 relative to AT1 sites. However, another AT2-selective antagonist, CGP42112A, showed little affinity for these sites. Both classes of binding sites were inhibited by guanosine 5'-O-(3-thiophosphate) and pertussis toxin treatment. We propose that there are two distinct G protein-coupled ANG II receptor subtypes (AT1A and AT1B) present in renal mesangial cells.

Signal transduction mediated by angiotensin II receptor subtypes expressed in rat renal mesangial cells

1993 ◽  
Vol 44 (2) ◽  
pp. 149-157 ◽  
Author(s):  
Zuhayr T. Madhun ◽  
Paul Ernsberger ◽  
Ferng-Chun Ke ◽  
Jie Zhou ◽  
Ulrich Hopfer ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Angiotensin Ii ◽  
Mesangial Cells ◽  
Receptor Subtypes ◽  
Angiotensin Ii Receptor ◽  
Angiotensin Ii Receptor Subtypes

Intracrine action of angiotensin II in mesangial cells: subcellular distribution of angiotensin II receptor subtypes AT1 and AT2

2018 ◽  
Vol 448 (1-2) ◽  
pp. 265-274 ◽  
Author(s):  
Antônio da Silva Novaes ◽  
Rosemara Silva Ribeiro ◽  
Luciana Guilhermino Pereira ◽  
Fernanda Teixeira Borges ◽  
Mirian Aparecida Boim
Keyword(s):  
Angiotensin Ii ◽  
Subcellular Distribution ◽  
Mesangial Cells ◽  
Receptor Subtypes ◽  
Angiotensin Ii Receptor ◽  
Angiotensin Ii Receptor Subtypes

Nephrogenesis and angiotensin II receptor subtypes gene expression in the fetal lamb

1998 ◽  
Vol 274 (6) ◽  
pp. F1062-F1069 ◽  
Author(s):  
Valérie Gimonet ◽  
Laurence Bussieres ◽  
Anissa A. Medjebeur ◽  
Bernard Gasser ◽  
Brigitte Lelongt ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Mrna Expression ◽  
Mesangial Cells ◽  
Temporal Distribution ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Developmental Study ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Fetal Lamb

To investigate the role of angiotensin II (ANG II) in nephrogenesis, a developmental study of renal AT1 and AT2 receptor mRNA expression was performed in parallel with the quantitative and qualitative analysis of metanephros development in fetal lamb from 60 to 140 days of gestation. Both ANG II receptor subtypes were expressed early during nephrogenesis but displayed specific spatial and temporal distribution during gestation. High-AT2 mRNA expression took place in the outermost nephrogenic area and in the undifferentiated mesenchymal cells surrounding the ampulla; level of AT2 expression in this localization followed closely glomeruli proliferation rate and disappeared after nephrogenesis completion (>120 days). AT2 mRNA was also detected in the differentiated epithelial cells of macula densa of maturing glomeruli. Although most of AT1 mRNA labeling was found in the mesangial cells of maturing glomeruli, where it persisted after nephrogenesis completion, additional labeling was found in undifferentiated cells, in cells invading the inferior cleft of S-shaped bodies (80 days), and in medullar cells between tubules (120 days). Our results suggest that each receptor subtype has a specific role in renal morphogenesis, i.e., AT2 in mesenchymal proliferation or apoptosis and AT1 in vascular smooth muscle cells differentiation.

Regulation of Angiotensin II Receptor Subtypes by Dexamethasone in Rat Mesangial Cells

Hypertension ◽  
1996 ◽  
Vol 27 (4) ◽  
pp. 867-874 ◽  
Author(s):  
Dominique Chansel ◽  
Catherine Llorens-Cortes ◽  
Sophie Vandermeersch ◽  
Paul Pham ◽  
Raymond Ardaillou
Keyword(s):  
Angiotensin Ii ◽  
Mesangial Cells ◽  
Receptor Subtypes ◽  
Angiotensin Ii Receptor ◽  
Angiotensin Ii Receptor Subtypes

Analysis of Angiotensin II Receptor Subtypes in Individual Rat Brain Nuclei

1992 ◽  
Vol 55 (5) ◽  
pp. 563-573 ◽  
Author(s):  
Brian P. Rowe ◽  
David L. Saylor ◽  
Robert C. Speth
Keyword(s):  
Angiotensin Ii ◽  
Rat Brain ◽  
Receptor Subtypes ◽  
Angiotensin Ii Receptor ◽  
Brain Nuclei ◽  
Angiotensin Ii Receptor Subtypes

Effects of endothelium-derived relaxing factor and nitric oxide on rat mesangial cells

1990 ◽  
Vol 258 (1) ◽  
pp. F162-F167 ◽  
Author(s):  
P. J. Shultz ◽  
A. E. Schorer ◽  
L. Raij
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Mesangial Cells ◽  
Specific Inhibitor ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Functional Responses ◽  
Cross Sectional ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

We have investigated whether endothelium-derived relaxing factor (EDRF) and nitric oxide (NO), a substance proposed to be one of the EDRFs, could elicit biochemical and biological responses in rat glomerular mesangial cells (MC). In wells with MC alone, guanosine 3',5'-cyclic monophosphate (cGMP) levels were 2.6 +/- 0.6 fmol/microgram protein, and bradykinin did not affect these levels, whereas in coincubation experiments with bovine aortic EC and rat MC, cGMP levels in MC increased to 44.6 +/- 21 fmol/micrograms protein after bradykinin stimulation (P less than 0.05). This effect was potentiated by superoxide dismutase and inhibited by hemoglobin and L-NG-monomethyl arginine, a specific inhibitor of EDRF synthesis. Increases in cGMP were also observed when MC were incubated directly with NO and were potentiated by superoxide dismutase and inhibited by hemoglobin. We also tested whether NO could inhibit angiotensin II (ANG II)-induced reductions in cross-sectional area (CSA) of MC. When MC were exposed to ANG II only, 65% of the cells underwent a significant reduction in CSA, as measured by digital image analysis. However, when MC were incubated with ANG II and NO, only 10% of cells responded (P less than 0.04). These studies demonstrate that EDRF and NO induce significant biochemical and functional responses in rat glomerular MC and suggest that communication between EC and MC may be important in regulation of glomerular function.

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