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Protein Kinase C Modulation of Cyclic GMP in Rat Neonatal Pulmonary Vascular Smooth Muscle

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Abstract

Protein kinase C (PKC) has been implicated in the control of vascular tone and mitogenesis in the adult pulmonary vasculature, but little is known about the role of PKC in the neonatal pulmonary vasculature. In addition, the vasodilator nitric oxide (NO) is important in the transition of the pulmonary circulation from fetal to postnatal life, and it is thought that attenuated production of NO and therefore, cGMP may contribute to the pathophysiology of a variety of forms of neonatal pulmonary vascular disease states. Although evidence exists for an interaction between PKC and NO in the adult pulmonary vasculature, the identification of specific roles for PKC in neonatal pulmonary vascular smooth muscle (NPVSM) has not been determined, and no studies have been done on the modulation of cGMP by PKC in NPVSM. Accordingly, immunoblot analysis revealed the expression of the α, δ, ε, and ι PKC isozymes in NPVSM. Treatment of NPVSM with 10nM 4-β phorbol myristate acetate (PMA), a PKC activator, induced translocation of PKCα, and PKCδ from the soluble to the particulate fraction, while exposure to 10nM endothelin-1 (ET-1), a potent vasoconstrictor and mitogenic substance, caused translocation of PKCδ and PKCι from the soluble to the particulate fraction. Sodium nitroprusside (SNP) significantly increased intracellular cGMP levels, an effect attenuated by PMA but not by ET-1. In addition, pretreatment with the specific PKC isozyme antagonist Go 6983 blocked the effect of PMA on cGMP levels. Collectively, these data demonstrate the expression and activation of multiple PKC isozymes in NPVSM, and indicate that PKC inhibits SNP-stimulated cGMP production in NPVSM. These data also suggest that complex intracellular signaling pathways by specific PKC isozymes may be important in the development of neonatal pulmonary vascular function.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, School of Medicine, The Program in Synapses and Cell Signaling, Institute of Molecular Medicine, Medical College of Georgia, Augusta, Georgia 30912, USA

    J. A. Johnson & S. A. Barman

  2. Department of Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA

    J. A. Johnson

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  1. J. A. Johnson
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  2. S. A. Barman
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Johnson, J., Barman, S. Protein Kinase C Modulation of Cyclic GMP in Rat Neonatal Pulmonary Vascular Smooth Muscle . Lung 182, 79–89 (2004). https://doi.org/10.1007/s00408-003-1046-6

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