Decrease of platelet aggregation and spreading via inhibition of the cAMP phosphodiesterase by trapidil

FEBS Letters

Tkachuk, V.A.¹  Menshikov, M.Yu.¹  Mazurov, A.V.¹  Repin, V.S.¹  Leytin, V.L.¹ 

[1] USSR Cardiology Research Center, Academy of Medical Sciences, 3rd Cherepkovskaya str. 15a, Moscow 121552, USSR

关键词: Platelet aggregation;    Platelet adhesion;    Phosphodiesterase inhibitor;    cAMP Trapidil;    Abbreviations: AA;    arachidonic acid;    PG;    prostaglan- din(s);    TXA2;    thromboxane A2;    PDE;    phosphodiester-ase;    PRP;    platelet-rich plasma;   

DOI  :  10.1016/0014-5793(84)81119-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Trapidil (N,N-diethyl-5-methyl[l,2,4]triazolo[l,5-α]pyrimidine-7-amine) inhibits platelet spreading and aggregation induced by arachidonic acid (AA), a stable analogue of prostaglandin (PG) endoperoxides (U46619), ADP, and low concentrations of thrombin, but not by A23187 and high concentrations of thrombin. Trapidil does not affect platelet adenylate cyclase but inhibits the cAMP PDE by approx. 50%. PDE inhibition proceeds via a competitive mechanism (K _i = 0.52 mM) and is not mediated by calmodulin inhibition. Trapidil does not change the platelet basal cAMP level but potentiates an increase of cAMP induced by the stable prostacyclin analogue (6β-PGI_i). These results suggest that trapidil antiplatelet effects may be due to the inhibition of platelet PDE.

【 授权许可】

Unknown