Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor

Nature ◽  
1995 ◽  
Vol 375 (6528) ◽  
pp. 247-250 ◽  
Author(s):  
Mario B. Marrero ◽  
Bernhard Schieffer ◽  
William G. Paxton ◽  
Lauri Heerdt ◽  
Bradford C. Berk ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
At1 Receptor ◽  
Direct Stimulation ◽  
Stimulation Of ◽  
Stat Pathway

Angiotensin II stimulation of phospholipase D in rat renal mesangial cells is mediated by the AT1 receptor subtype

1992 ◽  
Vol 225 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Josef Pfeilschifter ◽  
Andrea Huwiler ◽  
Claire Merriweather ◽  
Vreny A. Briner
Keyword(s):  
Angiotensin Ii ◽  
Phospholipase D ◽  
Mesangial Cells ◽  
At1 Receptor ◽  
Receptor Subtype ◽  
Stimulation Of

Angiotensin II stimulates sodium-dependent proton extrusion in perfused ferret heart

1996 ◽  
Vol 270 (6) ◽  
pp. C1687-C1694 ◽  
Author(s):  
A. A. Grace ◽  
J. C. Metcalfe ◽  
P. L. Weissberg ◽  
H. W. Bethell ◽  
J. I. Vandenberg
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Tissue ◽  
At1 Receptor ◽  
Intracellular Acidosis ◽  
Physiological Homeostasis ◽  
Cellular Dysfunction ◽  
Acid Loading ◽  
Contractile Recovery ◽  
Ferret Heart ◽  
Stimulation Of

The Na+/H+ antiport and Na(+)-HCO3- coinflux carrier contribute to recovery from intracellular acidosis in cardiac tissue. The effects of angiotensin II (10(-12)-10(-6) M) on H+ fluxes after intracellular acid loading and during reperfusion after myocardial ischemia have been investigated in the isovolumic, Langendorff-perfused ferret heart. Intracellular pH (pHi) was estimated using 31P nuclear magnetic resonance (NMR) spectroscopy from the chemical shift of intracellular deoxyglucose-6-phosphate or inorganic phosphate. Angiotensin II produced concentration-dependent stimulation (maximum at 10(-6) M: 67%) of 5-(N-ethyl-N-isopropyl)amiloride (EIPA)-sensitive Na(+)-dependent of H+ efflux consistent with stimulation of the Na+/H+ antiport. Half-maximal stimulation of H+ efflux occurred at approximately 10(-9) M, which is close to the dissociation constant of the cardiac angiotensin AT1 receptor. Stimulation via this receptor was confirmed with the nonpeptide AT1 receptor blocker, GR-117289. Angiotensin II had less pronounced effects on HCO3(-)-dependent pHi recovery after acid loading with no effect on pHi recovery after intracellular alkalosis. During reperfusion, angiotensin II significantly increased H+ extrusion but impaired contractile recovery. The results support the hypothesis that angiotensin II facilitates H+ extrusion in the heart. This may help maintain physiological homeostasis, but the hypothesized obligated Na+ influx could exacerbate cellular dysfunction during reperfusion.

Angiotensin II type 1 receptor modulation of neuronal K+ and Ca2+ currents: intracellular mechanisms

1996 ◽  
Vol 271 (1) ◽  
pp. C154-C163 ◽  
Author(s):  
C. Sumners ◽  
M. Zhu ◽  
C. H. Gelband ◽  
P. Posner
Keyword(s):  
Angiotensin Ii ◽  
At1 Receptor ◽  
Ang Ii ◽  
Receptor Modulation ◽  
Kinase C ◽  
Intracellular Messengers ◽  
Voltage Dependent ◽  
K Current ◽  
Stimulation Of

Angiotensin II (ANG II) elicits an ANG II type 1 (AT1) receptor-mediated decrease in voltage-dependent K+ current (Ik) and an incrase in voltage-dependent Ca2+ current (ICa) in neurons cocultured from newborn rat hypothalamus and brain stem. Modulation of these currents by ANG II involves intracellular messengers that result from an AT1 receptor-mediated stimulation of phosphoinositide hydrolysis. For example, the effects of ANG II on IK and ICa were abolished by phospholipase C antagonists. The reduction in IK produced by ANG II was attenuated by either protein kinase C (PKC) antagonists or by chelation of intracellular Ca2+. By contrast, PKC antagonism abolished the stimulatory effect of ANG II on ICa. Superfusion of the PKC activator phorbol 12-myristate 13-acetate produced effects on IK and ICa similar to those observed after ANG II. Furthermore, intracellular application of inositol 1,4,5-trisphosphate (IP3) elicited a significant reduction in IK. This suggests that the AT1 receptor-mediated changes in neuronal K+ and Ca2+ currents involve PKC (both IK and ICa) and IP3 and/or intracellular Ca2+ (IK).

Down-regulation of ether-a-go-go-related gene potassium channel protein through sustained stimulation of AT1 receptor by angiotensin II

2014 ◽  
Vol 452 (3) ◽  
pp. 852-857 ◽  
Author(s):  
Yue Cai ◽  
Yuhong Wang ◽  
Jia Xu ◽  
Xu Zuo ◽  
Yanfang Xu
Keyword(s):  
Angiotensin Ii ◽  
Potassium Channel ◽  
At1 Receptor ◽  
Related Gene ◽  
Down Regulation ◽  
Channel Protein ◽  
Stimulation Of

scholarly journals Direct Stimulation of Angiotensin II Type 2 Receptor Enhances Spatial Memory

2011 ◽  
Vol 32 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Fei Jing ◽  
Masaki Mogi ◽  
Akiko Sakata ◽  
Jun Iwanami ◽  
Kana Tsukuda ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Angiotensin Ii ◽  
Neurite Outgrowth ◽  
Hippocampal Neurons ◽  
Receptor Agonist ◽  
Laser Speckle ◽  
Morris Water Maze Test ◽  
Direct Stimulation ◽  
Stimulation Of

We examined the possibility that direct stimulation of the angiotensin II type 2 (AT2) receptor by a newly generated direct AT2 receptor agonist, Compound 21 (C21), enhances cognitive function. Treatment with C21 intraperitoneal injection for 2 weeks significantly enhanced cognitive function evaluated by the Morris water maze test in C57BL6 mice, but this effect was not observed in AT2 receptor-deficient mice. However, C21-induced cognitive enhancement in C57BL6 mice was attenuated by coadministration of icatibant, a bradykinin B2 receptor antagonist. Administration of C21 dose dependently increased cerebral blood flow assessed by laser speckle flowmetry and hippocampal field-excitatory postsynaptic potential (f-EPSP) determined by electrophysiological techniques in C57BL6 mice. Furthermore, activation of the AT2 receptor by C21 promoted neurite outgrowth of cultured hippocampal neurons prepared from fetal transgenic mice expressing green fluorescent protein. Finally, we investigated the pathologic relevance of C21 for spatial learning using an Alzheimer's disease mouse model with intracerebroventricular injection of amyloid-β (1 to 40). We observed that treatment with C21 prevented cognitive decline in this model. These results suggest that a direct AT2 receptor agonist, C21, enhances cognitive function at least owing to an increase in CBF, enhancement of f-EPSP, and neurite outgrowth in hippocampal neurons.

scholarly journals Angiotensin II stimulates phosphorylation of an ectodomain-truncated platelet-derived growth factor receptor-β and its binding to class IA PI3K in vascular smooth muscle cells

2006 ◽  
Vol 397 (2) ◽  
pp. 337-344 ◽  
Author(s):  
Ben-Bo Gao ◽  
Hans Hansen ◽  
Hong-Chi Chen ◽  
Edward P. Feener
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Growth Factor Receptor ◽  
At1 Receptor ◽  
Dominant Negative ◽  
Platelet Derived Growth Factor ◽  
Ang Ii ◽  
Stimulation Of

PI3K (phosphoinositide 3-kinase) activity is involved in Ang (angiotensin) II-stimulated VSMC (vascular smooth muscle cell) growth and hypertrophy. In the present study, we demonstrate that the inhibition of PI3K in VSMCs by expression of a dominant-negative p85α mutant lacking the p110-binding domain (Δp85), or by treatment of cells with LY294002, inhibited Ang II-stimulated PAI-1 (plasminogen activator inhibitor-1) mRNA expression. Using a GST (glutathione S-transferase) fusion protein containing the p85 N-terminal SH2 (Src homology 2) domain as ‘bait’ followed by MS/MS (tandem MS), we identified a 70 kDa fragment of the p70 PDGFR-β (platelet-derived growth factor receptor-β) as a signalling adapter that is phosphorylated and recruits the p85 subunit of PI3K after Ang II stimulation of AT1 (Ang II subtype 1) receptors on VSMCs. This fragment of the PDGFR-β, which has a truncation of its extracellular domain, accounted for approx. 15% of the total PDGFR-β detected in VSMCs with an antibody against its cytoplasmic domain. Stimulation of VSMCs with Ang II increased tyrosine-phosphorylation of p70 PDGFR-β at Tyr751 and Tyr1021 and increased its binding to p85. PDGF also induced phosphorylation of p70 PDGFR-β, a response inhibited by the PDGF tyrosine kinase selective inhibitor, AG1296. By contrast, Ang II-induced phosphorylation of the 70 kDa receptor was not affected by AG1296. Ang II-stimulated phosphorylation of the p70 PDGFR-β was blocked by the AT1 receptor antagonist, candesartan (CV 11974) and was partially inhibited by PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine}, an Src family kinase inhibitor. Our result suggests that the p70 PDGFR-β functions as an adapter that recruits PI3K to the membrane upon AT1 receptor stimulation.

Angiotensin II stimulation of the stress-activated protein kinases in renal mesangial cells is mediated by the angiotensin AT1 receptor subtype

1998 ◽  
Vol 343 (2-3) ◽  
pp. 297-302 ◽  
Author(s):  
Andrea Huwiler ◽  
Gerda van Rossum ◽  
Markus Wartmann ◽  
Josef Pfeilschifter
Keyword(s):  
Angiotensin Ii ◽  
Protein Kinases ◽  
Mesangial Cells ◽  
At1 Receptor ◽  
Receptor Subtype ◽  
Stimulation Of

Pressor action and dipsogenicity induced by angiotensin II and III in rats

1985 ◽  
Vol 249 (5) ◽  
pp. R514-R521 ◽  
Author(s):  
J. W. Wright ◽  
S. L. Morseth ◽  
R. H. Abhold ◽  
J. W. Harding
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Receptor Site ◽  
Circumventricular Organs ◽  
Ang Ii ◽  
Direct Stimulation ◽  
Arterial Infusion ◽  
Appropriate Treatment ◽  
Angiotensin Iii ◽  
Stimulation Of

The primary brain sites responsible for angiotensin-induced pressor action and dipsogenicity in the laboratory rat appear to be located in forebrain circumventricular organs (CVO). Because CVOs have a reduced blood-brain barrier, intracarotid infusion of angiotensin via a brachial arterial catheter results in direct stimulation of these sites. This investigation determined that brachial arterial infusion of angiotensin II (ANG II) into alert free-moving rats resulted in pressor and dipsogenic responses greater than those observed with equivalent doses of angiotensin III (ANG III). However, intracerebroventricular (ICV) injections of ANG II and ANG III yielded equivalent pressor and drinking responses. ICV pretreatment with the specific angiotensin receptor antagonist [Sar1, Ile8]-ANG II significantly reduced ANG II- and ANG III-induced pressor and drinking responses. This inhibition lasted approximately 20 min with recovery at 60-70 min. The results indicate that ICV-administered ANG III is a much more potent ligand than previously determined if the stickiness due to electrical charge of this compound is prevented by appropriate treatment of glassware. The receptor antagonist results encourage the possibility that ANG II and ANG III activate a common central receptor site.

Mechanisms of ET-1 potentiation of angiotensin II stimulation of aldosterone production

1993 ◽  
Vol 265 (2) ◽  
pp. E179-E183 ◽  
Author(s):  
E. N. Cozza ◽  
C. E. Gomez-Sanchez
Keyword(s):  
Angiotensin Ii ◽  
Zona Glomerulosa ◽  
Ang Ii ◽  
Aldosterone Secretion ◽  
Direct Stimulation ◽  
Potentiation Effect ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Pkc Inhibitors ◽  
Stimulation Of

Endothelin-1 (ET-1) exerts the following two types of aldosterone-stimulating actions on glomerulosa cells: ET-1-mediated direct stimulation of aldosterone secretion (per se effect) and potentiation of the aldosterone secretion to angiotensin II (ANG II; potentiation effect). The role of Ca2+ and protein kinase C (PKC) systems in these two effects was investigated. Incubations of calf cultured adrenal zona glomerulosa cells in low-Ca2+ media or in the presence of the Ca2+ channel antagonist verapamil reduced the aldosterone secretion to ET-1. When cells were preincubated with ET-1 in a low-Ca2+ media or in the presence of the Ca2+ channel antagonist verapamil, washed, and incubated in media with normal Ca2+, ANG II showed potentiation of ANG II-stimulated aldosterone secretion. The PKC inhibitors H-7 and staurosporine did not decrease ET-1-stimulated aldosterone secretion, but they inhibited the potentiation effect of ET-1 on ANG II-mediated aldosterone secretion. Adrenocorticotropic hormone desensitization or prolonged phorbol ester stimulation of PKC resulting in desensitization also resulted in the abolition of the ET-1-mediated ANG II potentiation of aldosterone secretion. The PKC inhibitors did not affect ANG II-stimulated aldosterone secretion. We conclude that ET-1 exerts a direct stimulation of aldosterone secretion through a mechanism dependent on Ca2+ and potentiates ANG II-mediated aldosterone stimulation through a mechanism involving PKC.

scholarly journals Direct Stimulation of Angiotensin II Type 2 Receptor Initiated After Stroke Ameliorates Ischemic Brain Damage

2014 ◽  
Vol 27 (8) ◽  
pp. 1036-1044 ◽  
Author(s):  
Li-Juan Min ◽  
Masaki Mogi ◽  
Kana Tsukuda ◽  
Fei Jing ◽  
Kousei Ohshima ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Brain Damage ◽  
Direct Stimulation ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Stimulation Of
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