title: PKC inhibitors RO 31-8220 and Gö 6983 enhance epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation.
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.
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Sewoon
authors.initials: S
authors.lastname: Kim
authors.forename: Jeong Mi
authors.initials: JM
authors.lastname: Kim
authors.forename: Eek-hoon
authors.initials: EH
authors.lastname: Jho
authors.forename: Seonyang
authors.initials: S
authors.lastname: Park
authors.forename: Doyeun
authors.initials: D
authors.lastname: Oh
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Yun-Choi
mesh_terms: D000328:Adult; D000730:Androstadienes / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology*; D002395:Catecholamines / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008301:Maleimides; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013928:Thromboxane A2 / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002227:Carbazoles; D002395:Catecholamines; D004837:Epinephrine; D007211:Indoles; D008301:Maleimides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D013928:Thromboxane A2; D000077191:Wortmannin; C465664:2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide; C064758:Ro 31-8220