PKC inhibitors RO 31-8220 and Gö 6983 enhance epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation

BMB Rep. 2011 Feb;44(2):140-5. doi: 10.5483/BMBRep.2011.44.2.140.

Abstract

Impaired responsiveness of platelets to epinephrine (epi) and other catecholamines (CA) has been reported in approximately 20% of the healthy Korean and Japanese populations. In the present study, platelet aggregation induced by epi was potentiated by RO 31-8220 (RO) or Gö 6983 (Gö). Phosphorylated Akt (p-Akt) was very low in epi-stimulated PRP from CA-hypo-responders (CA-HY), whereas it was detected in those from CA-good responders (CA-GR). RO and Gö increased p-Akt, one of the major downstream effectors of phosphoinositol-3 kinase (PI3K), in epi-stimulated PRP from both groups. Wortmannin, a PI3K inhibitor, attenuated the RO or Gö-induced potentiation of p-Akt in epi-stimulated PRP, suggesting positive effects for RO and Gö on PI3K. TXA(2) formation was increased by the addition of either RO or Gö in epi-stimulated platelets. The present data also suggest that impaired Akt phosphorylation may be responsible for epinephrine hypo-responsiveness of platelets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Androstadienes / pharmacology
  • Carbazoles / pharmacology*
  • Catecholamines / pharmacology
  • Epinephrine / pharmacology*
  • Female
  • Humans
  • Indoles / pharmacology*
  • Male
  • Maleimides
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Platelet Aggregation / drug effects*
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase C / metabolism
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Thromboxane A2 / metabolism
  • Wortmannin

Substances

  • 2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide
  • Androstadienes
  • Carbazoles
  • Catecholamines
  • Indoles
  • Maleimides
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Thromboxane A2
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase C
  • Ro 31-8220
  • Wortmannin
  • Epinephrine