Blockade of ADP‐induced Ca2+‐signal and platelet aggregation by lipoxygenase inhibitors

FEBS Letters

L. Borin, M³  Ivanova, M.A.³  Azizova, O.A.³  Khodorov, B.I.¹  Markov, C.M.¹  Kudinov, Yu.V.²  Pinelis, V.G.² 

[1] Research Institute of General Pathology and Pathological Physiology USSR Academy of Medical Sciences, Moscow, USSR;Institute of Pediatry, USSR Academy of Medical Sciences, Moscow, USSR;Research Institute of Physico-chemical Medicine RSFSR, Ministry of Health, 119828 Moscow, USSR

关键词: Ca2+-signal;    Platelet aggregation;    Lipoxygenase inhibitor;    AA;    arachidonic acid;    LPG;    lipoxygenase;    TXAi;    thromboxane A2;    NDGA;    nordihydroguaiaretic acid;    12-HETE;    12-s-hydroxy-5;    8-cis-10'-trans-14-cis-eicosotetraenoic acid;    12-HPETE;    12-s-hydroperoxy-5;    8-cis-10'-trans-14-cis-eicosotetraenoic acid;    ACD;    acid-citrate-dextrose anticoagulant;   

DOI  :  10.1016/0014-5793(89)81567-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Stimulation of platelets results in the liberation of arachidonic acid (AA) which is further metabolized via the cyclooxygenase or lipoxygenase (LPG) pathway. We have examined the effect of inhibition of LPG on (i) the ADP-induced increase of cytoplasmic Ca²⁺ concentration and (ii) platelet aggregation. Lipoxygenase inhibitors, nordigidroguaiaretic acid (NDGA) and BW-755C, both suppressed ADP-induced Ca²⁺-signals and aggregation in a dose-dependent manner, with an IC₅₀ value of 1–2 μM for NDGA. Qualitatively the same effect was obtained with 4-bromophenylacyl bromide, the inhibitor of phospholipases A₂ and C. By contrast, cyclooxygenase inhibitor indomethacin had only a negligible effect on Ca²⁺-signals and suppressed only the second phase of ADP-induced aggregation. It is concluded that the LPG pathway of AA metabolism in platelets might play a crucial role in ADP-induced Ca²⁺-signal generation and platelet aggregation.

【 授权许可】

Unknown