THE ANTIPLATELET ACTIVITY OF RUTAECARPINE, AN ALKALOID ISOLATED FROM EVODIA-RUTAECARPA, IS MEDIATED THROUGH INHIBITION OF PHOSPHOLIPASE-C

In this study, the mechanism involved in the antiplatelet activity of rutaecarpine in human platelet suspensions was investigated. In platel et suspensions (4.5 x 10(8)/ml), rutaecarpine (100 and 200 mu M) did n ot influence the binding of FITC-triflavin to platelet glycoprotein II b/IIIa complex. Additionally, rutaecarpine (200 mu M) did not signific antly change the fluorescence of platelet membrane labeled with diphen ylhexatriene (DPH), On the other hand, rutaecarpine (50 and 100 mu M) dose-dependently inhibited the increase in intracellular free Ca2+ of Fura 2-AM loaded platelets stimulated by collagen. Moreover, rutaecarp ine (100 and 200 mu M) did not significantly affect the thromboxane sy nthetase activity of aspirin-treated platelet microsomes, Furthermore, retaecarpine (100 and 200 mu M) significantly inhibited [H-3]arachido nic acid released in collagen-activated platelets but not in unactivat ed-platelets. Nitric oxide (NO) production in human platelets was meas ured by a chemiluminesence detection method in this study. Rutaecarpin e (100 and 200 mu M) did not significantly affect nitrate production i n collagen (10 mu g/ml)- induced human platelet aggregation. On the ot her hand, various concentrations of rutaecarpine (50, 100, and 200 mu M) dose-dependently inhibited [H-3]inositol monophosphate formation st imulated by collagen (10 mu g/ml) in [H-3] myoinositol-loaded platelet s at different incubation times (1, 2, 3, and 5 minutes). It is conclu ded that the antiplatelet activity of rutaecarpine may possibly be due to the inhibition of phospholipase C activity, leading to reduce phos phoinositide breakdown, followed by the inhibition of thromboxane A(2) formation, and then inhibition of [Ca2+]i mobilization of platelet ag gregation stimulated by agonists. (C) 1998 Elsevier Science Ltd.