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Cyclic nucleotide and protein kinase signaling in hypertensive pulmonary arterial smooth muscle
Current Respiratory Medicine Reviews
  • Scott A. Barman
  • Shu Zhu, Philadelphia College of Osteopathic Medicine
  • Richard E. White
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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. © 2006 Bentham Science Publishers Ltd.

This article was published in Current Respiratory Medicine Reviews, Volume 2, Issue 1, Pages 15-25.

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Copyright © 2006 Scopus.

Citation Information
Scott A. Barman, Shu Zhu and Richard E. White. "Cyclic nucleotide and protein kinase signaling in hypertensive pulmonary arterial smooth muscle" Current Respiratory Medicine Reviews Vol. 2 Iss. 1 (2006) p. 15 - 25
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