Signaling Pathway in the Osmotic Resistance Induced by Angiotensin II AT2 Receptor Activation in Human Erythrocytes

Abstract Adrenal steroidogenesis is modulated by humoral and neuronal factors and blood flow. Angiotensin II (AII) stimulates adrenal cortical aldosterone and cortisol production and medullary catecholamine release. However, AII regulation of adrenal vascular tone has not been characterized. We examined the effect of AII on diameters of cannulated bovine adrenal cortical arteries. Cortical arteries (average internal diameter = 230 μm) were constricted with U46619 and concentration-diameter responses to AII (10−13 to 10−8 mol/liter) were measured. In endothelium-intact arteries, AII induced dilations at low concentrations (maximum dilation = 25 ± 6% at 10−10 mol/liter) and constrictions at high concentrations (maximum constriction = 25 ± 18% at 10−8 mol/liter). AII constrictions were blocked by the angiotensin type 1 (AT1) receptor antagonist, losartan (10−6 mol/liter). AII dilations were enhanced by losartan (maximal dilation = 48 ± 8%), abolished by endothelial cell removal or N-nitro-l-arginine (L-NA, 3 × 10−5 mol/liter) and inhibited by the angiotensin type 2 (AT2) receptor antagonist, PD123319 (10−6 mol/liter, maximal dilation = 18 ± 4%). In a 4,5-diaminofluorescein diacetate nitric oxide (NO) assay of isolated cortical arteries, AII stimulated NO production, which was abolished by PD123319, L-NA, or endothelial cell removal. Western immunoblot of arterial homogenates and endothelial and zona glomerulosa cell lysates revealed 48-kD and 50-kD bands corresponding to AT1 and AT2 receptors, respectively, in all three and a 140-kD band corresponding to endothelial NO synthase in endothelial cells and arteries. Our results demonstrate that AII stimulates adrenal cortical arterial dilation through endothelial cell AT2 receptor activation and NO release and AT1 receptor-dependent constriction.

Download Full-text

Faculty Opinions recommendation of Angiotensin II AT2 receptor activation attenuates AT1 receptor-induced increases in the glomerular filtration of albumin: a multiphoton microscopy study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718075985.793487971 ◽

2013 ◽

Author(s):

Janos Peti-Peterdi

Keyword(s):

Angiotensin Ii ◽

Glomerular Filtration ◽

Multiphoton Microscopy ◽

Microscopy Study ◽

Receptor Activation ◽

At1 Receptor ◽

At2 Receptor

Download Full-text

Regulation of angiotensin II receptors beyond the classical pathway

Clinical Science ◽

10.1042/cs20110677 ◽

2012 ◽

Vol 123 (4) ◽

pp. 193-203 ◽

Cited By ~ 59

Author(s):

Masatsugu Horiuchi ◽

Jun Iwanami ◽

Masaki Mogi

Keyword(s):

Angiotensin Ii ◽

Cross Talk ◽

Receptor Activation ◽

At1 Receptor ◽

Receptor Subtypes ◽

Peroxisome Proliferator ◽

Classical Pathway ◽

At2 Receptor ◽

Peroxisome Proliferator Activated Receptor ◽

The Metabolic Syndrome

The RAS (renin–angiotensin system) plays a role not only in the cardiovascular system, including blood pressure regulation, but also in the central nervous system. AngII (angiotensin II) binds two major receptors: the AT1 receptor (AngII type 1 receptor) and AT2 receptor (AngII type 2 receptor). It has been recognized that AT2 receptor activation not only opposes AT1 receptor actions, but also has unique effects beyond inhibitory cross-talk with AT1 receptor signalling. Novel pathways beyond the classical actions of RAS, the ACE (angiotensin-converting enzyme)/AngII/AT1 receptor axis, have been highlighted: the ACE2/Ang-(1–7) [angiotensin-(1–7)]/Mas receptor axis as a new opposing axis against the ACE/AngII/AT1 receptor axis, novel AngII-receptor-interacting proteins and various AngII-receptor-activation mechanisms including dimer formation. ATRAP (AT1-receptor-associated protein) and ATIP (AT2-receptor-interacting protein) are well-characterized AngII-receptor-associated proteins. These proteins could regulate the functions of AngII receptors and thereby influence various pathophysiological states. Moreover, the possible cross-talk between PPAR (peroxisome-proliferator-activated receptor)-γ and AngII receptor subtypes is an intriguing issue to be addressed in order to understand the roles of RAS in the metabolic syndrome, and interestingly some ARBs (AT1-receptor blockers) have been reported to have an AT1-receptor-blocking action with a partial PPAR-γ agonistic effect. These emerging concepts concerning the regulation of AngII receptors are discussed in the present review.

Download Full-text

Angiotensin II AT2 receptors are functionally coupled to protein tyrosine dephosphorylation in N1E-115 neuroblastoma cells

Biochemical Journal ◽

10.1042/bj3060087 ◽

1995 ◽

Vol 306 (1) ◽

pp. 87-92 ◽

Cited By ~ 44

Author(s):

C Nahmias ◽

S M Cazaubon ◽

M M Briend-Sutren ◽

D Lazard ◽

P Villageois ◽

...

Keyword(s):

Angiotensin Ii ◽

Rank Order ◽

Neuroblastoma Cells ◽

Receptor Activation ◽

Receptor Subtype ◽

At2 Receptor ◽

Ang Ii ◽

Single Class ◽

Protein Tyrosine ◽

At2 Receptors

Murine N1E-115 neuroblastoma cells are shown to express a single class of angiotensin II (Ang II) receptors that display all the pharmacological properties defining the Ang II receptor subtype 2 (AT2): high affinity for 125I-labelled AT2-selective agonist CGP 42112 (Kd 91 +/- 19 pM); expected rank order of potency (CGP 42112 = (Sar1,Ile8)Ang II > or = Ang II > PD 123319 >> DUP 753) for several Ang II analogues; increased binding in the presence of the reducing reagent dithiothreitol (DTT); and insensitivity to analogues of GTP. Molecular cloning of cDNA encoding AT2 receptors from N1E-115 cells reveals nucleotide sequence identity with the AT2 subtype expressed in fetal tissue. Murine AT2 receptors transiently expressed in COS cells display the same pharmacological profile as endogenous Ang II receptors of N1E-115 cells. Taken together, these data reveal the exclusive presence of the AT2 receptor subtype in N1E-115 cells. Incubation of N1E-115 cells with Ang II leads to a marked decrease in the level of tyrosine phosphorylation of several proteins with apparent molecular masses of 80, 97, 120, 150 and 180 kDa respectively. Tyrosine dephosphorylation of the same set of proteins is observed after treatment with the AT2-specific agonist CGP 42112. The response to both effectors is rapid and transient, showing a maximum between 5 and 10 min, and returning to basal levels after 20-30 min. In both cases, tyrosine dephosphorylation can be prevented by co-incubation with an excess of the antagonist Sarile. These data thus establish that AT2 receptor activation leads to protein tyrosine dephosphorylation in N1E-115 cells, and support a possible role for AT2 receptors in the negative regulation of cell proliferation.

Download Full-text

A novel mechanism of mechanical stress-induced angiotensin II type 1–receptor activation without the involvement of angiotensin II

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-007-0215-1 ◽

2007 ◽

Vol 377 (4-6) ◽

pp. 393-399 ◽

Cited By ~ 38

Author(s):

Noritaka Yasuda ◽

Hiroshi Akazawa ◽

Yingjie Qin ◽

Yunzeng Zou ◽

Issei Komuro

Keyword(s):

Angiotensin Ii ◽

Mechanical Stress ◽

Receptor Activation

Download Full-text

Lipid signal transduction pathways in angiotensin II type 1 receptor-transfected fibroblasts

AJP Cell Physiology ◽

10.1152/ajpcell.1995.269.2.c435 ◽

1995 ◽

Vol 269 (2) ◽

pp. C435-C442 ◽

Cited By ~ 19

Author(s):

Y. Wen ◽

M. C. Cabot ◽

E. Clauser ◽

S. L. Bursten ◽

J. L. Nadler

Keyword(s):

Signal Transduction ◽

Angiotensin Ii ◽

Chinese Hamster ◽

Receptor Activation ◽

Signal Transduction Pathways ◽

Ang Ii ◽

Vascular Type ◽

Lipid Signal ◽

Fibroblast Line

A stable Chinese hamster ovary fibroblast line expressing the rat vascular type 1a angiotensin II (ANG II) receptor was used to study the lipid-derived signal transduction pathways elicited by type 1a ANG II receptor activation. ANG II caused a biphasic and dose-dependent increase in diacylglycerol (DAG) accumulation with an initial peak at 15 s (181 +/- 11% of control, P < 0.02) and a second sustained peak at 5-10 min (214 +/- 10% of control, P < 0.02). The late DAG peak was derived from phosphatidylcholine (PC), and the formation was blocked by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. ANG II also increased phosphatidic acid (PA) production nearly fourfold by 7.5 min. In the presence of ethanol, ANG II markedly increased phosphatidylethanol (PEt) formation, indicating activation of phospholipase D (PLD). ANG II was shown to increase the mass of three separate PA species, one of which apparently originated from DAG kinase action on PC-phospholipase C (PLC)-produced DAG, providing evidence for PC-PLC activity. ANG II also formed a third PA species, which originated neither from PLD nor from DAG kinase. These results demonstrate that multiple lipid signals propagated via collateral stimulation of PLC and PLD are generated by specific activation of the vascular type 1a ANG II receptor.

Download Full-text