Effects of selective phosphodiesterase type IV inhibitor, rolipram, on signal transducing phospholipases in neutrophil: inhibition of phospholipases A2, D but not C

Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1995 Oct;112(2):137-43. doi: 10.1016/0742-8413(95)02005-5.


The effects of a selective phosphodiesterase (PDE) type IV inhibitor, rolipram, on activation of neutrophil phospholipases in response to the chemotactic peptide formyl-methiony-leucyl-phenylalanine (fMLP) were investigated. fMLP caused liberation of arachidonic acid, a precursor of eicosanoids and in the presence of 0.3% butanol, production of phosphatidylbutanol, an indicator of phospholipase D activation. Rolipram inhibited arachidonic acid release and phosphatidylbutanol formation. The inhibition was considered to be mediated through a cAMP-dependent mechanism, probably protein kinase A, because selective inhibitors for protein kinase A, H-8 or H-89 overcame the action of rolipram. The concentration-dependent inhibitory profile for phospholipase D activation was similar to that for lysosomal enzyme release, providing additional evidence for the functional link of these two events. In contrast, rolipram was without effect on fMLP-induced inositol trisphosphate production. These results indicate that this selective PDE IV inhibitor had no effect on phosphatidylinositol-specific phospholipase C activation but effectively prevented activation of phospholipases A2 and D coupled to arachidonic acid liberation and lysosomal enzyme release, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism
  • Enzyme Inhibitors / pharmacology
  • In Vitro Techniques
  • Inositol Phosphates / metabolism
  • Isoquinolines / pharmacology
  • Male
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / drug effects
  • Neutrophils / enzymology*
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phospholipase D / antagonists & inhibitors
  • Phospholipases / antagonists & inhibitors*
  • Phospholipases A / antagonists & inhibitors
  • Protein Kinase Inhibitors
  • Pyrrolidinones / pharmacology*
  • Rats
  • Rats, Wistar
  • Rolipram
  • Signal Transduction / drug effects*
  • Sulfonamides*
  • Type C Phospholipases / antagonists & inhibitors


  • Enzyme Inhibitors
  • Inositol Phosphates
  • Isoquinolines
  • Phosphodiesterase Inhibitors
  • Protein Kinase Inhibitors
  • Pyrrolidinones
  • Sulfonamides
  • Arachidonic Acid
  • N-Formylmethionine Leucyl-Phenylalanine
  • Phospholipases
  • Phospholipases A
  • Type C Phospholipases
  • Phospholipase D
  • Rolipram
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide