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

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).

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

Down-regulation of cardiac AT1 receptor expression and angiotensin II concentration after chronic blockade of the renin-angiotensin system in cardiomyopathic hamsters

1999 ◽  
Vol 5 (3) ◽  
pp. 62
Author(s):  
Chantal Lambert ◽  
Natacha R. Bastien ◽  
Marc J. Servant ◽  
Jolanta Gutkowska ◽  
Sylvain Meloche
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Down Regulation ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Cardiomyopathic Hamsters

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

scholarly journals Post-Transcriptional Control of Human Ether-a-go-go-Related Gene Potassium Channel Protein by α-Adrenergic Receptor Stimulation

2010 ◽  
Vol 78 (2) ◽  
pp. 186-197 ◽  
Author(s):  
Jian Chen ◽  
Kun Chen ◽  
Jakub Sroubek ◽  
Zhi-Yuan Wu ◽  
Dierk Thomas ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Adrenergic Receptor ◽  
Transcriptional Control ◽  
Related Gene ◽  
Receptor Stimulation ◽  
Channel Protein

Stimulation of ACTH and GH release by angiotensin II in normal men is mediated by the AT1 receptor subtype

1998 ◽  
Vol 74 (1) ◽  
pp. 27-30 ◽  
Author(s):  
V. Coiro ◽  
R. Volpi ◽  
L. Capretti ◽  
G. Caffarri ◽  
R. Colla ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
At1 Receptor ◽  
Receptor Subtype ◽  
Normal Men ◽  
Stimulation Of

scholarly journals Stimulation of N-Terminal Truncated Isoform of Androgen Receptor Stabilizes Human Ether-á-go-go-Related Gene-Encoded Potassium Channel Protein via Activation of Extracellular Signal Regulated Kinase 1/2

Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 5061-5069 ◽  
Author(s):  
Zhi-Yuan Wu ◽  
Kun Chen ◽  
Bernard Haendler ◽  
Thomas V. McDonald ◽  
Jin-Song Bian
Keyword(s):  
Androgen Receptor ◽  
Long Qt Syndrome ◽  
Hek293 Cells ◽  
K Channel ◽  
Protein Abundance ◽  
Related Gene ◽  
Long Qt ◽  
Channel Protein ◽  
Qt Syndrome ◽  
Stimulation Of

Proarrhythmic drugs induce long QT syndrome more frequently in women than men. The present study was designed to determine whether androgens regulate the function and expression of the human ether-á-go-go-related gene (HERG) encoded K+ channel, which is largely responsible for determining the QT interval. In a concentration-dependent manner (10−9 to 10−6m for 24 h), 5α-dihydrotestosterone (5α-DHT) increased HERG protein abundance in HEK293 cells stably expressing HERG in the presence of coexpressed cardiac androgen receptor (AR) variant [N-terminal truncated isoform of AR (AR45)]. The elevation of HERG protein was seen in endoplasmic reticulum, Golgi, and plasma membrane without clear preferential colocalization. Coexpression of the more common form of the AR did not confer 5α-DHT augmentation of HERG protein. Proteasome inhibitors, N-acetyl-L-leucyl-L-leucyl-L-norleucinal and MG132 prevented the 5α-DHT- dependent enhancement of HERG, as did the lysosome inhibitor, bafilomycin A1. Consistently, the cycloheximide-based protein chase study showed that 5α-DHT prolonged HERG protein half-life. 5α-DHT/AR45 signaling induced phosphorylation of ERK1/2. Blockade of ERK1/2 with PD98059 and U0126 prevented the effect of androgen on HERG protein abundance. Functional studies showed that 5α-DHT treatment for 24 h increased HERG K+ current density in Chinese hamster ovary cells cotransfected with cDNAs of AR45 and HERG channels. Moreover, 5α-DHT also increased ether-á-go-go-related gene-encoded K+ channel protein abundance in isolated rabbit cardiac myocytes. In conclusion, these data provide evidence that stimulation of AR45 receptors by androgens up-regulates HERG K+ channel abundance and activity mainly through stabilizing HERG protein in an ERK1/2 dependent mechanism, and suggest a mechanism to explain the sex difference in the long QT syndrome.

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