title: Evaluation of the antiplatelet effects of cilostazol, a phosphodiesterase 3 inhibitor, by VASP phosphorylation and platelet aggregation.
abstract: BACKGROUND
  Cilostazol, a phosphodiesterase 3 inhibitor, is an antiplatelet drug that is widely used for preventing cardiovascular events, although, to date, there are few methods for evaluating its effects.
  
  
  RESULTS
  Blood samples were taken at baseline and at 3 and 12 h in 10 healthy male subjects after 100 mg cilostazol intake. Each sample was examined by Western blot for phosphorylation levels of vasodilator-stimulated phosphoprotein (VASP), an abundant cAMP-dependent kinase substrate in platelets, and by the optical aggregometer for ADP- and collagen-induced aggregation, before and after 8 nmol/L prostaglandin E(1) (PGE(1)) treatment. Cilostazol intake did not affect VASP phosphorylation levels or the maximal aggregation rates without PGE(1) treatment. However, cilostazol intake apparently enhanced PGE(1)-induced VASP phosphorylation and PGE(1)-mediated reduction of ADP-and collagen-induced maximal aggregation rates. Levels of VASP phosphorylated at Ser157 were correlated and the maximal aggregation rates induced by ADP were inversely correlated with cilostazol concentrations in the plasma.
  
  
  CONCLUSIONS
  The antiplatelet effects of cilostazol intake could be evaluated by measuring VASP phosphorylation levels and maximal aggregation rates in platelets by ex vivo treatment with a low concentration of PGE(1).
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Honmachi, Sakyo-ku, Kyoto, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kanako
authors.initials: K
authors.lastname: Takahashi
authors.forename: Haruyo
authors.initials: H
authors.lastname: Watanabe
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Shirakawa
authors.forename: Tomohito
authors.initials: T
authors.lastname: Higashi
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Kawato
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ikeda
authors.forename: Arata
authors.initials: A
authors.lastname: Tabuchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Morimoto
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Hisanori
authors.initials: H
authors.lastname: Horiuchi
mesh_terms: D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D000077407:Cilostazol; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D058987:Phosphodiesterase 3 Inhibitors; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D013777:Tetrazoles / Q000008:administration & dosage*; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D058987:Phosphodiesterase 3 Inhibitors; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000098662:Vasodilator-Stimulated Phosphoprotein; D000527:Alprostadil; D000077407:Cilostazol