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 (BKCa) 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 BKCa channels. Treatment widi 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.

Original languageEnglish (US)
Pages (from-to)67-79
Number of pages13
JournalCurrent Topics in Pharmacology
Volume10
Issue number1
StatePublished - Dec 1 2006

Fingerprint

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

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

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

In: Current Topics in Pharmacology, Vol. 10, No. 1, 01.12.2006, p. 67-79.

Research output: Contribution to journalReview article

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