Cyclic nucleotide and protein kinase signaling in hypertensive pulmonary arterial smooth muscle

Scott A Barman, Shu Zhu, Richard E. White

Research output: Contribution to journalReview article

Abstract

The signaling mechanisms defining the role of protein kinases in pulmonary vascular physiology regulation is an area of great interest. Normally, signaling mechanisms which elevate cyclic AMP (cAMP) and cyclic GMP (cGMP) maintain the pulmonary vasculature in a relaxed state. Modulation of large-conductance, calcium- and voltage-activated potassium (BK Ca ) channels is important in the regulation of pulmonary arterial pressure and inhibition of BK Ca channels is implicated in the development of pulmonary hypertension. Accordingly, studies done in pulmonary arterial smooth muscle cells of the Fawn-Hooded rat, a recognized animal model of pulmonary hypertension, shows that cAMP opens BK Ca channels. Treatment with KT5823, a selective inhibitor of cGMP-dependent protein kinase (PKG) inhibits the effect of cAMP. In contrast, blocking cAMP-dependent protein kinase (PKA) with KT5720 has no effect indicating that cAMP activates BK Ca channels via PKG-dependent and PKA-independent signaling pathways which suggests 'cross-activation' between cyclic nucleotide-dependent protein kinases in hypertensive pulmonary arterial smooth muscle. In addition, protein kinase C (PKC) activation inhibits the BK Ca channel response to cAMP, which is blocked by the specific PKC isozyme inhibitors Gö 6983, and Gö 6976. These studies indicate that specific PKC isozymes inhibit cAMP-induced activation of BK Ca . channels via PKG in hypertensive pulmonary arterial smooth muscle.

Original languageEnglish (US)
Pages (from-to)15-25
Number of pages11
JournalCurrent Respiratory Medicine Reviews
Volume2
Issue number1
DOIs
StatePublished - Feb 1 2006

Fingerprint

Large-Conductance Calcium-Activated Potassium Channels
Cyclic Nucleotides
Cyclic AMP
Protein Kinases
Smooth Muscle
Lung
Protein Kinase C
Pulmonary Hypertension
Isoenzymes
Cyclic GMP-Dependent Protein Kinases
Cyclic GMP
Cyclic AMP-Dependent Protein Kinases
Smooth Muscle Myocytes
Blood Vessels
Potassium
Arterial Pressure
Animal Models
Calcium

Keywords

  • BK channels
  • Cyclic AMP
  • Protein kinase C
  • Pulmonary hypertension
  • cGMP-dependent protein kinase

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Cyclic nucleotide and protein kinase signaling in hypertensive pulmonary arterial smooth muscle. / Barman, Scott A; Zhu, Shu; White, Richard E.

In: Current Respiratory Medicine Reviews, Vol. 2, No. 1, 01.02.2006, p. 15-25.

Research output: Contribution to journalReview article

@article{31de5b2e9ca84063ac9eb01e072f5be1,
title = "Cyclic nucleotide and protein kinase signaling in hypertensive pulmonary arterial smooth muscle",
abstract = "The signaling mechanisms defining the role of protein kinases in pulmonary vascular physiology regulation is an area of great interest. Normally, signaling mechanisms which elevate cyclic AMP (cAMP) and cyclic GMP (cGMP) maintain the pulmonary vasculature in a relaxed state. Modulation of large-conductance, calcium- and voltage-activated potassium (BK Ca ) channels is important in the regulation of pulmonary arterial pressure and inhibition of BK Ca channels is implicated in the development of pulmonary hypertension. Accordingly, studies done in pulmonary arterial smooth muscle cells of the Fawn-Hooded rat, a recognized animal model of pulmonary hypertension, shows that cAMP opens BK Ca channels. Treatment with KT5823, a selective inhibitor of cGMP-dependent protein kinase (PKG) inhibits the effect of cAMP. In contrast, blocking cAMP-dependent protein kinase (PKA) with KT5720 has no effect indicating that cAMP activates BK Ca channels via PKG-dependent and PKA-independent signaling pathways which suggests 'cross-activation' between cyclic nucleotide-dependent protein kinases in hypertensive pulmonary arterial smooth muscle. In addition, protein kinase C (PKC) activation inhibits the BK Ca channel response to cAMP, which is blocked by the specific PKC isozyme inhibitors G{\"o} 6983, and G{\"o} 6976. These studies indicate that specific PKC isozymes inhibit cAMP-induced activation of BK Ca . channels via PKG in hypertensive pulmonary arterial smooth muscle.",
keywords = "BK channels, Cyclic AMP, Protein kinase C, Pulmonary hypertension, cGMP-dependent protein kinase",
author = "Barman, {Scott A} and Shu Zhu and White, {Richard E.}",
year = "2006",
month = "2",
day = "1",
doi = "10.2174/157339806775486155",
language = "English (US)",
volume = "2",
pages = "15--25",
journal = "Current Respiratory Medicine Reviews",
issn = "1573-398X",
publisher = "Bentham Science Publishers B.V.",
number = "1",

}

TY - JOUR

T1 - Cyclic nucleotide and protein kinase signaling in hypertensive pulmonary arterial smooth muscle

AU - Barman, Scott A

AU - Zhu, Shu

AU - White, Richard E.

PY - 2006/2/1

Y1 - 2006/2/1

N2 - The signaling mechanisms defining the role of protein kinases in pulmonary vascular physiology regulation is an area of great interest. Normally, signaling mechanisms which elevate cyclic AMP (cAMP) and cyclic GMP (cGMP) maintain the pulmonary vasculature in a relaxed state. Modulation of large-conductance, calcium- and voltage-activated potassium (BK Ca ) channels is important in the regulation of pulmonary arterial pressure and inhibition of BK Ca channels is implicated in the development of pulmonary hypertension. Accordingly, studies done in pulmonary arterial smooth muscle cells of the Fawn-Hooded rat, a recognized animal model of pulmonary hypertension, shows that cAMP opens BK Ca channels. Treatment with KT5823, a selective inhibitor of cGMP-dependent protein kinase (PKG) inhibits the effect of cAMP. In contrast, blocking cAMP-dependent protein kinase (PKA) with KT5720 has no effect indicating that cAMP activates BK Ca channels via PKG-dependent and PKA-independent signaling pathways which suggests 'cross-activation' between cyclic nucleotide-dependent protein kinases in hypertensive pulmonary arterial smooth muscle. In addition, protein kinase C (PKC) activation inhibits the BK Ca channel response to cAMP, which is blocked by the specific PKC isozyme inhibitors Gö 6983, and Gö 6976. These studies indicate that specific PKC isozymes inhibit cAMP-induced activation of BK Ca . channels via PKG in hypertensive pulmonary arterial smooth muscle.

AB - The signaling mechanisms defining the role of protein kinases in pulmonary vascular physiology regulation is an area of great interest. Normally, signaling mechanisms which elevate cyclic AMP (cAMP) and cyclic GMP (cGMP) maintain the pulmonary vasculature in a relaxed state. Modulation of large-conductance, calcium- and voltage-activated potassium (BK Ca ) channels is important in the regulation of pulmonary arterial pressure and inhibition of BK Ca channels is implicated in the development of pulmonary hypertension. Accordingly, studies done in pulmonary arterial smooth muscle cells of the Fawn-Hooded rat, a recognized animal model of pulmonary hypertension, shows that cAMP opens BK Ca channels. Treatment with KT5823, a selective inhibitor of cGMP-dependent protein kinase (PKG) inhibits the effect of cAMP. In contrast, blocking cAMP-dependent protein kinase (PKA) with KT5720 has no effect indicating that cAMP activates BK Ca channels via PKG-dependent and PKA-independent signaling pathways which suggests 'cross-activation' between cyclic nucleotide-dependent protein kinases in hypertensive pulmonary arterial smooth muscle. In addition, protein kinase C (PKC) activation inhibits the BK Ca channel response to cAMP, which is blocked by the specific PKC isozyme inhibitors Gö 6983, and Gö 6976. These studies indicate that specific PKC isozymes inhibit cAMP-induced activation of BK Ca . channels via PKG in hypertensive pulmonary arterial smooth muscle.

KW - BK channels

KW - Cyclic AMP

KW - Protein kinase C

KW - Pulmonary hypertension

KW - cGMP-dependent protein kinase

UR - http://www.scopus.com/inward/record.url?scp=33745833979&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745833979&partnerID=8YFLogxK

U2 - 10.2174/157339806775486155

DO - 10.2174/157339806775486155

M3 - Review article

VL - 2

SP - 15

EP - 25

JO - Current Respiratory Medicine Reviews

JF - Current Respiratory Medicine Reviews

SN - 1573-398X

IS - 1

ER -