The effect of 3-[2-(cyclopropylamino)ethoxy]xanthone on platelet thromboxane formation
Journal
Thrombosis Research
Journal Volume
75
Journal Issue
1
Pages
81-90
Date Issued
1994
Author(s)
Abstract
A synthetic xanthone derivative, 3-[2-(cyclopropylamino)ethoxy] xanthone (CPEX), was investigated for its antiplatelet activities in washed rabbit platelets and human platelet-rich plasma. CPEX inhibited concentration-dependently the aggregation and ATP release of rabbit platelets caused by arachidonic acid (AA; 100 microM) and collagen (10 micrograms/ml), but not those by thrombin (0.1 U/ml), PAF (2 ng/ml), and U46619 (1 microM). The IC50 value of CPEX on AA-induced aggregation was 10.9 +/- 2.1 microM (n = 7). Thromboxane B2 formations caused by AA, collagen, and thrombin were inhibited by CPEX (20 microM), and prostaglandin D2 formation caused by AA was also inhibited. In human platelet-rich plasma, CPEX specifically inhibited the secondary aggregation and the release reaction induced by epinephrine (5 microM) and ADP (3 microM). CPEX also inhibited AA- and collagen-induced inositol-phosphate formation in [3H]myo-inositol-labeled platelets and intracellular Ca2+ increase in fura-2/AM-loaded platelets, respectively, without affecting those induced by PAF, thrombin, and U46619 in the presence of indomethacin (5 microM). These data suggest that the antiplatelet effect of CPEX is due to an inhibitory effect on the cyclooxygenase and then leads to the decrease of thromboxane formation.
SDGs
Type
journal article