The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts. / Aplin, Mark; Christensen, Gitte Lund; Schneider, Mikael; Heydorn, Arne; Gammeltoft, Steen; Kjølbye, Anne Louise; Sheikh, Søren P; Hansen, Jakob Lerche.

In: Basic & Clinical Pharmacology & Toxicology, Vol. 100, No. 5, 05.2007, p. 289-95.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Aplin, M, Christensen, GL, Schneider, M, Heydorn, A, Gammeltoft, S, Kjølbye, AL, Sheikh, SP & Hansen, JL 2007, 'The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts', Basic & Clinical Pharmacology & Toxicology, vol. 100, no. 5, pp. 289-95. https://doi.org/10.1111/j.1742-7843.2007.00063.x

APA

Aplin, M., Christensen, G. L., Schneider, M., Heydorn, A., Gammeltoft, S., Kjølbye, A. L., Sheikh, S. P., & Hansen, J. L. (2007). The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts. Basic & Clinical Pharmacology & Toxicology, 100(5), 289-95. https://doi.org/10.1111/j.1742-7843.2007.00063.x

Vancouver

Aplin M, Christensen GL, Schneider M, Heydorn A, Gammeltoft S, Kjølbye AL et al. The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts. Basic & Clinical Pharmacology & Toxicology. 2007 May;100(5):289-95. https://doi.org/10.1111/j.1742-7843.2007.00063.x

Author

Aplin, Mark ; Christensen, Gitte Lund ; Schneider, Mikael ; Heydorn, Arne ; Gammeltoft, Steen ; Kjølbye, Anne Louise ; Sheikh, Søren P ; Hansen, Jakob Lerche. / The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts. In: Basic & Clinical Pharmacology & Toxicology. 2007 ; Vol. 100, No. 5. pp. 289-95.

Bibtex

@article{6ab582975ab949ef8caf651d2eab38d4,
title = "The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts",
abstract = "The angiotensin II (AngII) type 1 receptor (AT(1)R) has been shown to activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) through G proteins or G protein-independently through beta-arrestin2 in cellular expression systems. As activation mechanisms may greatly influence the biological effects of ERK1/2 activity, differential activation of the AT(1)R in its native cellular context could have important biological and pharmacological implications. To examine if AT(1)R activates ERK1/2 by G protein-independent mechanisms in the heart, we used the [Sar(1), Ile(4), Ile(8)]-AngII ([SII] AngII) analogue in native preparations of cardiac myocytes and beating hearts. We found that [SII] AngII does not activate G(q)-coupling, yet stimulates the beta-arrestin2-dependent ERK1/2. The G(q)-activated pool of ERK1/2 rapidly translocates to the nucleus, while the beta-arrestin2-scaffolded pool remains in the cytosol. Similar biased agonism was achieved in Langendorff-perfused hearts, where both agonists elicit ERK1/2 phosphorylation, but [SII] AngII induces neither inotropic nor chronotropic effects.",
keywords = "1-Sarcosine-8-Isoleucine Angiotensin II, Angiotensin II, Animals, Animals, Newborn, Arrestins, Cell Nucleus, Cells, Cultured, Coronary Circulation, Cytosol, GTP-Binding Proteins, Heart Rate, Heart Ventricles, Male, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Muscle Contraction, Myocardium, Myocytes, Cardiac, Perfusion, Rats, Rats, Sprague-Dawley, Rats, Wistar, Receptor, Angiotensin, Type 1",
author = "Mark Aplin and Christensen, {Gitte Lund} and Mikael Schneider and Arne Heydorn and Steen Gammeltoft and Kj{\o}lbye, {Anne Louise} and Sheikh, {S{\o}ren P} and Hansen, {Jakob Lerche}",
year = "2007",
month = may,
doi = "10.1111/j.1742-7843.2007.00063.x",
language = "English",
volume = "100",
pages = "289--95",
journal = "Basic and Clinical Pharmacology and Toxicology",
issn = "1742-7835",
publisher = "Wiley-Blackwell",
number = "5",

}

RIS

TY - JOUR

T1 - The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts

AU - Aplin, Mark

AU - Christensen, Gitte Lund

AU - Schneider, Mikael

AU - Heydorn, Arne

AU - Gammeltoft, Steen

AU - Kjølbye, Anne Louise

AU - Sheikh, Søren P

AU - Hansen, Jakob Lerche

PY - 2007/5

Y1 - 2007/5

N2 - The angiotensin II (AngII) type 1 receptor (AT(1)R) has been shown to activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) through G proteins or G protein-independently through beta-arrestin2 in cellular expression systems. As activation mechanisms may greatly influence the biological effects of ERK1/2 activity, differential activation of the AT(1)R in its native cellular context could have important biological and pharmacological implications. To examine if AT(1)R activates ERK1/2 by G protein-independent mechanisms in the heart, we used the [Sar(1), Ile(4), Ile(8)]-AngII ([SII] AngII) analogue in native preparations of cardiac myocytes and beating hearts. We found that [SII] AngII does not activate G(q)-coupling, yet stimulates the beta-arrestin2-dependent ERK1/2. The G(q)-activated pool of ERK1/2 rapidly translocates to the nucleus, while the beta-arrestin2-scaffolded pool remains in the cytosol. Similar biased agonism was achieved in Langendorff-perfused hearts, where both agonists elicit ERK1/2 phosphorylation, but [SII] AngII induces neither inotropic nor chronotropic effects.

AB - The angiotensin II (AngII) type 1 receptor (AT(1)R) has been shown to activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) through G proteins or G protein-independently through beta-arrestin2 in cellular expression systems. As activation mechanisms may greatly influence the biological effects of ERK1/2 activity, differential activation of the AT(1)R in its native cellular context could have important biological and pharmacological implications. To examine if AT(1)R activates ERK1/2 by G protein-independent mechanisms in the heart, we used the [Sar(1), Ile(4), Ile(8)]-AngII ([SII] AngII) analogue in native preparations of cardiac myocytes and beating hearts. We found that [SII] AngII does not activate G(q)-coupling, yet stimulates the beta-arrestin2-dependent ERK1/2. The G(q)-activated pool of ERK1/2 rapidly translocates to the nucleus, while the beta-arrestin2-scaffolded pool remains in the cytosol. Similar biased agonism was achieved in Langendorff-perfused hearts, where both agonists elicit ERK1/2 phosphorylation, but [SII] AngII induces neither inotropic nor chronotropic effects.

KW - 1-Sarcosine-8-Isoleucine Angiotensin II

KW - Angiotensin II

KW - Animals

KW - Animals, Newborn

KW - Arrestins

KW - Cell Nucleus

KW - Cells, Cultured

KW - Coronary Circulation

KW - Cytosol

KW - GTP-Binding Proteins

KW - Heart Rate

KW - Heart Ventricles

KW - Male

KW - Mitogen-Activated Protein Kinase 1

KW - Mitogen-Activated Protein Kinase 3

KW - Muscle Contraction

KW - Myocardium

KW - Myocytes, Cardiac

KW - Perfusion

KW - Rats

KW - Rats, Sprague-Dawley

KW - Rats, Wistar

KW - Receptor, Angiotensin, Type 1

U2 - 10.1111/j.1742-7843.2007.00063.x

DO - 10.1111/j.1742-7843.2007.00063.x

M3 - Journal article

C2 - 17448113

VL - 100

SP - 289

EP - 295

JO - Basic and Clinical Pharmacology and Toxicology

JF - Basic and Clinical Pharmacology and Toxicology

SN - 1742-7835

IS - 5

ER -

ID: 34167892