The catalytic subunit of protein kinase A triggers activation of the type V cyclic GMP-specific phosphodiesterase from guinea-pig lung

F Burns, I W Rodger, N J Pyne

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73 Citations (Scopus)

Abstract

The type V cyclic GMP phosphodiesterase was partially purified from the high-speed supernatant of guinea-pig lung. The isoenzyme displayed linear kinetics for cyclic GMP hydrolysis, with Km = 2.2 +/- 0.2 microM and Vmax. = 1.2 +/- 0.08 nmol/min per mg. The selective type V phosphodiesterase inhibitor Zaprinast inhibited cyclic GMP hydrolysis with IC50 (concn. giving 50% inhibition) = 0.45 +/- 0.08 microM. Isobutylmethylxanthine promoted a 3-fold increase in the binding of cyclic GMP to the isoenzyme. The addition of the catalytic subunit of protein kinase A to an activation cocktail containing the partially purified type V phosphodiesterase resulted in a marked increase in Vmax. for cyclic GMP hydrolysis (approximately 10-fold at 40 units of protein kinase A). We have suggested that protein kinase A triggers phosphorylation of the phosphodiesterase, which results in activation of phosphodiesterase activity. In addition, the sensitivity to inhibition by Zaprinast is severely decreased (the IC50 for inhibition is 7.5 +/- 1.1 microM), suggesting that the potency of phosphodiesterase inhibitors is effected by phosphorylation of the enzyme.
Original languageEnglish
Pages (from-to)487-491
Number of pages5
JournalBiochemical journal
Volume283
Issue number2
Publication statusPublished - 15 Apr 1992

Keywords

  • 3',5'-cyclic-AMP phosphodiesterases
  • 3',5'-cyclic-GMP phosphodiesterases
  • animals
  • chromatography, affinity
  • chromatography, ion exchange
  • cytosolic
  • enzyme activation
  • guinea pigs
  • isoenzymes
  • kinetics
  • lung
  • macromolecular substances
  • protein kinases
  • purinones
  • substrate specificity

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