Effect of phorbol esters on Ca2+ sensitivity and myosin light-chain phosphorylation in airway smooth muscle

Dorothee H. Bremerich, Tetsuya Kai, David O. Warner, Keith A. Jones

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

We studied in β-escin-permeabilized canine tracheal smooth muscle (CTSM) the effect of the protein kinase C (PKC) agonist phorbol 12,13- dibutyrate (PDBu) on isometric force at a constant submaximal Ca2+ concentration (i.e., the effect on Ca2+ sensitivity) and regulatory myosin light-chain (rMLC) phosphorylation. PDBu increased Ca2+ sensitivity, an increase associated with a concentration-dependent, sustained increase in rMLC phosphorylation. PDBu altered the relationship between rMLC phosphorylation and isometric force such that the increase in isometric force was less than that expected for the increase in rMLC phosphorylation observed. The effect of four PKC inhibitors [calphostin C, chelerythrine chloride, a pseudosubstrate inhibitor for PKC, PKC peptide-(19-31) (PSSI), and staurosporine] on PDBu-induced Ca2+ sensitization as well as the effect of calphostin C and PSSI on rMLC phosphorylation were determined. Whereas none of these compounds prevented or reversed the PDBu-induced increase in Ca2+ sensitivity, the PDBu-induced increase in rMLC phosphorylation was inhibited. We conclude that PDBu increases rMLC phosphorylation by activation of PKC but that the associated PDBu-induced increases in Ca2+ sensitivity are mediated by mechanisms other than activation of PKC in permeabilized airway smooth muscle.

Original languageEnglish (US)
Pages (from-to)C1253-C1260
JournalAmerican Journal of Physiology - Cell Physiology
Volume274
Issue number5 43-5
DOIs
StatePublished - May 1998

Keywords

  • Activator
  • Canine
  • Lung
  • Phorbol 12,13-dibutyrate
  • Protein kinase C
  • Protein kinase C inhibitors
  • Second messenger systems
  • Trachea
  • β-escin

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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