Role for PKC in the adenosine-induced decrease in shortening velocity of rat ventricular myocytes

J. William Lester, Polly Hofmann

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

We previously demonstrated that both adenosine receptor activation and direct activation of protein kinase C (PKC) decrease unloaded shortening velocity (V(max)) of rat ventricular myocytes. The goal of this study was to further investigate a possible link among adenosine receptors, phosphoinositide-PKC signaling, and V(max) in rat ventricular myocytes. We determined that the adenosine receptor agonist R-phenylisopropyladenosine (R-PIA, 100 μM) and the α-adrenergic receptor agonist phenylephrine (Phe, 10 μM) increased turnover of inositol phosphates. PKC translocation from the cytosol to the sarcolemma was used as an indicator of PKC activation. Western blot analysis demonstrated an increased PKC-ε translocation after exposure to R-PIA, Phe, and the PKC activators dioctanoylglycerol (50 μM) and phorbol myristate acetate (1 μM). PKC-α, PKC-δ, and PKC-ζ did not translocate to the membrane after R-PIA exposure. Finally, PKC inhibitors blocked R-PIA-induced decreases in V(max) as well as Ca 2+ -dependent actomyosin ATPase in rat ventricular myocytes. These results support the conclusions that adenosine receptors activate phosphoinositide-PKC signaling and that adenosine receptor-induced PKC activation mediates a decrease in V(max) in ventricular myocytes.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number6 48-6
StatePublished - Dec 1 2000

Fingerprint

Adenosine
Muscle Cells
Protein Kinase C
Purinergic P1 Receptors
1-Phosphatidylinositol 4-Kinase
Phenylisopropyladenosine
Purinergic P1 Receptor Agonists
Sarcolemma
Adrenergic Agonists
Inositol Phosphates
Protein C Inhibitor
Phenylephrine
Tetradecanoylphorbol Acetate
Myosins
Protein Kinase Inhibitors
Cytosol
Western Blotting
Membranes
N-(1-methyl-2-phenylethyl)adenosine

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

@article{7c5478b7e4564f0fbf4cd712c8b33c38,
title = "Role for PKC in the adenosine-induced decrease in shortening velocity of rat ventricular myocytes",
abstract = "We previously demonstrated that both adenosine receptor activation and direct activation of protein kinase C (PKC) decrease unloaded shortening velocity (V(max)) of rat ventricular myocytes. The goal of this study was to further investigate a possible link among adenosine receptors, phosphoinositide-PKC signaling, and V(max) in rat ventricular myocytes. We determined that the adenosine receptor agonist R-phenylisopropyladenosine (R-PIA, 100 μM) and the α-adrenergic receptor agonist phenylephrine (Phe, 10 μM) increased turnover of inositol phosphates. PKC translocation from the cytosol to the sarcolemma was used as an indicator of PKC activation. Western blot analysis demonstrated an increased PKC-ε translocation after exposure to R-PIA, Phe, and the PKC activators dioctanoylglycerol (50 μM) and phorbol myristate acetate (1 μM). PKC-α, PKC-δ, and PKC-ζ did not translocate to the membrane after R-PIA exposure. Finally, PKC inhibitors blocked R-PIA-induced decreases in V(max) as well as Ca 2+ -dependent actomyosin ATPase in rat ventricular myocytes. These results support the conclusions that adenosine receptors activate phosphoinositide-PKC signaling and that adenosine receptor-induced PKC activation mediates a decrease in V(max) in ventricular myocytes.",
author = "Lester, {J. William} and Polly Hofmann",
year = "2000",
month = "12",
day = "1",
language = "English (US)",
volume = "279",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "6 48-6",

}

TY - JOUR

T1 - Role for PKC in the adenosine-induced decrease in shortening velocity of rat ventricular myocytes

AU - Lester, J. William

AU - Hofmann, Polly

PY - 2000/12/1

Y1 - 2000/12/1

N2 - We previously demonstrated that both adenosine receptor activation and direct activation of protein kinase C (PKC) decrease unloaded shortening velocity (V(max)) of rat ventricular myocytes. The goal of this study was to further investigate a possible link among adenosine receptors, phosphoinositide-PKC signaling, and V(max) in rat ventricular myocytes. We determined that the adenosine receptor agonist R-phenylisopropyladenosine (R-PIA, 100 μM) and the α-adrenergic receptor agonist phenylephrine (Phe, 10 μM) increased turnover of inositol phosphates. PKC translocation from the cytosol to the sarcolemma was used as an indicator of PKC activation. Western blot analysis demonstrated an increased PKC-ε translocation after exposure to R-PIA, Phe, and the PKC activators dioctanoylglycerol (50 μM) and phorbol myristate acetate (1 μM). PKC-α, PKC-δ, and PKC-ζ did not translocate to the membrane after R-PIA exposure. Finally, PKC inhibitors blocked R-PIA-induced decreases in V(max) as well as Ca 2+ -dependent actomyosin ATPase in rat ventricular myocytes. These results support the conclusions that adenosine receptors activate phosphoinositide-PKC signaling and that adenosine receptor-induced PKC activation mediates a decrease in V(max) in ventricular myocytes.

AB - We previously demonstrated that both adenosine receptor activation and direct activation of protein kinase C (PKC) decrease unloaded shortening velocity (V(max)) of rat ventricular myocytes. The goal of this study was to further investigate a possible link among adenosine receptors, phosphoinositide-PKC signaling, and V(max) in rat ventricular myocytes. We determined that the adenosine receptor agonist R-phenylisopropyladenosine (R-PIA, 100 μM) and the α-adrenergic receptor agonist phenylephrine (Phe, 10 μM) increased turnover of inositol phosphates. PKC translocation from the cytosol to the sarcolemma was used as an indicator of PKC activation. Western blot analysis demonstrated an increased PKC-ε translocation after exposure to R-PIA, Phe, and the PKC activators dioctanoylglycerol (50 μM) and phorbol myristate acetate (1 μM). PKC-α, PKC-δ, and PKC-ζ did not translocate to the membrane after R-PIA exposure. Finally, PKC inhibitors blocked R-PIA-induced decreases in V(max) as well as Ca 2+ -dependent actomyosin ATPase in rat ventricular myocytes. These results support the conclusions that adenosine receptors activate phosphoinositide-PKC signaling and that adenosine receptor-induced PKC activation mediates a decrease in V(max) in ventricular myocytes.

UR - http://www.scopus.com/inward/record.url?scp=0034529136&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034529136&partnerID=8YFLogxK

M3 - Article

VL - 279

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 6 48-6

ER -