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

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. Wort-mannin, 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. TXA₂ formation was increased by the addition of either RO or Gö in epi-stimulated platelets. The present data also suggest that impaired Akt phosphor-ylation may be responsible for epinephrine hypo-responsiveness of platelets.