title: 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.
authors.affiliation: Research Institute of Physico-chemical Medicine RSFSR, Ministry of Health, Moscow, USSR.
authors.forename: M L
authors.initials: ML
authors.lastname: Borin
authors.forename: V G
authors.initials: VG
authors.lastname: Pinelis
authors.forename: M A
authors.initials: MA
authors.lastname: Ivanova
authors.lastname: Kudinov YuV
authors.forename: O A
authors.initials: OA
authors.lastname: Azizova
authors.forename: C M
authors.initials: CM
authors.lastname: Markov
authors.forename: B I
authors.initials: BI
authors.lastname: Khodorov
mesh_terms: D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001095:Arachidonic Acids; D016859:Lipoxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; D002118:Calcium; D007213:Indomethacin