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The MLCK-mediated alpha1-adrenergic inotropic effect in atrial myocardium is negatively modulated by PKCepsilon signaling.

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The MLCK-mediated alpha1-adrenergic inotropic effect in atrial myocardium is negatively modulated by PKCepsilon signaling. / Grimm, Michael; Mahnecke, Nina; Soja, Friederike; El-Armouche, Ali; Haas, Pascal; Treede, Hendrik; Reichenspurner, Hermann; Eschenhagen, Thomas.

In: BRIT J PHARMACOL, Vol. 148, No. 7, 7, 2006, p. 991-1000.

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

Harvard

Grimm, M, Mahnecke, N, Soja, F, El-Armouche, A, Haas, P, Treede, H, Reichenspurner, H & Eschenhagen, T 2006, 'The MLCK-mediated alpha1-adrenergic inotropic effect in atrial myocardium is negatively modulated by PKCepsilon signaling.', BRIT J PHARMACOL, vol. 148, no. 7, 7, pp. 991-1000. <http://www.ncbi.nlm.nih.gov/pubmed/16783412?dopt=Citation>

APA

Grimm, M., Mahnecke, N., Soja, F., El-Armouche, A., Haas, P., Treede, H., Reichenspurner, H., & Eschenhagen, T. (2006). The MLCK-mediated alpha1-adrenergic inotropic effect in atrial myocardium is negatively modulated by PKCepsilon signaling. BRIT J PHARMACOL, 148(7), 991-1000. [7]. http://www.ncbi.nlm.nih.gov/pubmed/16783412?dopt=Citation

Vancouver

Grimm M, Mahnecke N, Soja F, El-Armouche A, Haas P, Treede H et al. The MLCK-mediated alpha1-adrenergic inotropic effect in atrial myocardium is negatively modulated by PKCepsilon signaling. BRIT J PHARMACOL. 2006;148(7):991-1000. 7.

Bibtex

@article{11600e8ac1f14db7a7b6b647d9b5d630,
title = "The MLCK-mediated alpha1-adrenergic inotropic effect in atrial myocardium is negatively modulated by PKCepsilon signaling.",
abstract = "The present study examined the role of myosin light chain kinase (MLCK), PKC isozymes, and inositol 1,4,5-trisphosphate (IP(3)) receptor in the positive inotropic effect of alpha(1)-adrenergic stimulation in atrial myocardium.We measured inotropic effects of phenylephrine (0.3-300 microM) in isolated left atrial preparations (1 Hz, 37 degrees C, 1.8 mM Ca(2+), 0.3 microM nadolol) from male 8-week FVB mice (n=200). Phenylephrine concentration-dependently increased force of contraction from 1.5+/-0.1 to 2.8+/-0.1 mN (mean+/-s.e.m., n=42), which was associated with increased MLC-2a phosphorylation at serine 21 and 22 by 67% and translocation of PKCepsilon but not PKCalpha to membrane (+30%) and myofilament (+50%) fractions.MLCK inhibition using ML-7 or wortmannin right-shifted the concentration-response curve of phenylephrine, reducing its inotropic effect at 10 microM by 73% and 81%, respectively.The compound KIE1-1 (500 nM), an intracellularly acting PKCepsilon translocation inhibitor peptide, prevented PKCepsilon translocation and augmented the maximal inotropic effect of phenylephrine by 40%. In contrast, inhibition of Ca(2+)-dependent PKC translocation (KIC1-1, 500 nM) had no effect. Chelerythrine, a PKC inhibitor, decreased basal force without changing the inotropic effect of phenylephrine.The IP(3) receptor blocker 2-APB (2 and 20 microM) concentration-dependently decreased basal force, but did not affect the concentration-response curve of phenylephrine.These results indicate that activation of MLCK is required for the positive inotropic effect of alpha(1)-adrenergic stimulation, that the Ca(2+)-independent PKCepsilon negatively modulates this effect, and that PKCalpha and IP(3) receptor activation is not involved.",
author = "Michael Grimm and Nina Mahnecke and Friederike Soja and Ali El-Armouche and Pascal Haas and Hendrik Treede and Hermann Reichenspurner and Thomas Eschenhagen",
year = "2006",
language = "Deutsch",
volume = "148",
pages = "991--1000",
journal = "BRIT J PHARMACOL",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "7",

}

RIS

TY - JOUR

T1 - The MLCK-mediated alpha1-adrenergic inotropic effect in atrial myocardium is negatively modulated by PKCepsilon signaling.

AU - Grimm, Michael

AU - Mahnecke, Nina

AU - Soja, Friederike

AU - El-Armouche, Ali

AU - Haas, Pascal

AU - Treede, Hendrik

AU - Reichenspurner, Hermann

AU - Eschenhagen, Thomas

PY - 2006

Y1 - 2006

N2 - The present study examined the role of myosin light chain kinase (MLCK), PKC isozymes, and inositol 1,4,5-trisphosphate (IP(3)) receptor in the positive inotropic effect of alpha(1)-adrenergic stimulation in atrial myocardium.We measured inotropic effects of phenylephrine (0.3-300 microM) in isolated left atrial preparations (1 Hz, 37 degrees C, 1.8 mM Ca(2+), 0.3 microM nadolol) from male 8-week FVB mice (n=200). Phenylephrine concentration-dependently increased force of contraction from 1.5+/-0.1 to 2.8+/-0.1 mN (mean+/-s.e.m., n=42), which was associated with increased MLC-2a phosphorylation at serine 21 and 22 by 67% and translocation of PKCepsilon but not PKCalpha to membrane (+30%) and myofilament (+50%) fractions.MLCK inhibition using ML-7 or wortmannin right-shifted the concentration-response curve of phenylephrine, reducing its inotropic effect at 10 microM by 73% and 81%, respectively.The compound KIE1-1 (500 nM), an intracellularly acting PKCepsilon translocation inhibitor peptide, prevented PKCepsilon translocation and augmented the maximal inotropic effect of phenylephrine by 40%. In contrast, inhibition of Ca(2+)-dependent PKC translocation (KIC1-1, 500 nM) had no effect. Chelerythrine, a PKC inhibitor, decreased basal force without changing the inotropic effect of phenylephrine.The IP(3) receptor blocker 2-APB (2 and 20 microM) concentration-dependently decreased basal force, but did not affect the concentration-response curve of phenylephrine.These results indicate that activation of MLCK is required for the positive inotropic effect of alpha(1)-adrenergic stimulation, that the Ca(2+)-independent PKCepsilon negatively modulates this effect, and that PKCalpha and IP(3) receptor activation is not involved.

AB - The present study examined the role of myosin light chain kinase (MLCK), PKC isozymes, and inositol 1,4,5-trisphosphate (IP(3)) receptor in the positive inotropic effect of alpha(1)-adrenergic stimulation in atrial myocardium.We measured inotropic effects of phenylephrine (0.3-300 microM) in isolated left atrial preparations (1 Hz, 37 degrees C, 1.8 mM Ca(2+), 0.3 microM nadolol) from male 8-week FVB mice (n=200). Phenylephrine concentration-dependently increased force of contraction from 1.5+/-0.1 to 2.8+/-0.1 mN (mean+/-s.e.m., n=42), which was associated with increased MLC-2a phosphorylation at serine 21 and 22 by 67% and translocation of PKCepsilon but not PKCalpha to membrane (+30%) and myofilament (+50%) fractions.MLCK inhibition using ML-7 or wortmannin right-shifted the concentration-response curve of phenylephrine, reducing its inotropic effect at 10 microM by 73% and 81%, respectively.The compound KIE1-1 (500 nM), an intracellularly acting PKCepsilon translocation inhibitor peptide, prevented PKCepsilon translocation and augmented the maximal inotropic effect of phenylephrine by 40%. In contrast, inhibition of Ca(2+)-dependent PKC translocation (KIC1-1, 500 nM) had no effect. Chelerythrine, a PKC inhibitor, decreased basal force without changing the inotropic effect of phenylephrine.The IP(3) receptor blocker 2-APB (2 and 20 microM) concentration-dependently decreased basal force, but did not affect the concentration-response curve of phenylephrine.These results indicate that activation of MLCK is required for the positive inotropic effect of alpha(1)-adrenergic stimulation, that the Ca(2+)-independent PKCepsilon negatively modulates this effect, and that PKCalpha and IP(3) receptor activation is not involved.

M3 - SCORING: Zeitschriftenaufsatz

VL - 148

SP - 991

EP - 1000

JO - BRIT J PHARMACOL

JF - BRIT J PHARMACOL

SN - 0007-1188

IS - 7

M1 - 7

ER -