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Am J Physiol Lung Cell Mol Physiol 275: L827-L835, 1998;
1040-0605/98 $5.00
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Vol. 275, Issue 4, L827-L835, October 1998

Regulation of ciliary beat frequency by both PKA and PKG in bovine airway epithelial cells

T. A. Wyatt, J. R. Spurzem, K. May, and J. H. Sisson

Research Service, Department of Veterans Affairs Medical Center, Omaha 68105; and Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198

Ciliary beating is required for the maintenance of lung mucociliary transport. We investigated the role of cyclic nucleotide-dependent protein kinases in stimulating ciliary beat frequency (CBF) in bovine bronchial epithelial cells (BBECs). cAMP-dependent protein kinase (PKA) activity and cGMP-dependent protein kinase (PKG) activity were distinguished after DEAE-Sephacel chromatography of BBEC extracts. cAMP levels and PKA activity are increased in BBECs stimulated with 0.01-1 mM isoproterenol, with a corresponding increase in CBF. cGMP levels and PKG activity are increased in BBECs stimulated with 0.1-10 µM sodium nitroprusside, with a corresponding increase in CBF. Direct protein kinase-activating analogs of cAMP and cGMP (dibutyryl cAMP and 8-bromo-cGMP, respectively) also activate their specific kinases and stimulate CBF. Preincubation of BBECs with inhibitors of PKA or PKG [KT-5720 or Rp-8-(p-chlorophenylthio)-guanosine 3',5'-cyclic monophosphothioate] results in the inhibition of specific kinase activity as well as in the inhibition of CBF. These studies suggest that the activation of either PKA or PKG can lead to the stimulation of CBF in bovine airway epithelium.

adenosine 3',5'-cyclic monophosphate-dependent protein kinase; guanosine 3',5'-cyclic monophosphate-dependent protein kinase


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