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

Abstract:

: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 microM 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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Borin ML,Pinelis VG,Ivanova MA,Kudinov YuV,Azizova OA,Markov CM,Khodorov BI

doi

10.1016/0014-5793(89)81567-4

subject

Has Abstract

pub_date

1989-11-06 00:00:00

pages

345-7

issue

2

eissn

0014-5793

issn

1873-3468

journal_volume

257

pub_type

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