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 (BKCa) channels is important in the regulation of pulmonary arterial pressure and inhibition of BKCa 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 BKCa 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 BKCa 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 BKCa 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 BKCa channels via PKG in hypertensive pulmonary arterial smooth muscle.
Keywords: Cyclic AMP, BKCa channels, protein kinase C, cGMP-dependent protein kinase, pulmonary hypertension
Current Respiratory Medicine Reviews
Title: Cyclic Nucleotide and Protein Kinase Signaling in Hypertensive Pulmonary Arterial Smooth Muscle
Volume: 2 Issue: 1
Author(s): Scott A. Barman, Shu Zhu and Richard E. White
Affiliation:
Keywords: Cyclic AMP, BKCa channels, protein kinase C, cGMP-dependent protein kinase, pulmonary hypertension
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 (BKCa) channels is important in the regulation of pulmonary arterial pressure and inhibition of BKCa 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 BKCa 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 BKCa 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 BKCa 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 BKCa channels via PKG in hypertensive pulmonary arterial smooth muscle.
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Cite this article as:
Barman A. Scott, Zhu Shu and White E. Richard, Cyclic Nucleotide and Protein Kinase Signaling in Hypertensive Pulmonary Arterial Smooth Muscle, Current Respiratory Medicine Reviews 2006; 2 (1) . https://dx.doi.org/10.2174/157339806775486155
DOI https://dx.doi.org/10.2174/157339806775486155 |
Print ISSN 1573-398X |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6387 |
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