Mechanism of inhibition of platelet aggregation by rutaecarpine, an alkaloid isolated from Evodia rutaecarpa.
In this study, rutaecarpine was tested for its antiplatelet activities in human platelet-rich plasma. In human platelet-rich plasma, rutaecarpine (40-200 microM) inhibited aggregation stimulated by a variety of agonists (i.e., collagen, ADP, adrenaline and arachidonic acid). The antiplatelet activity of rutaecarpine (120 microM) was not significantly attenuated by pretreatment with the nitric oxide synthase inhibitor N(G)-mono-methyl-L-arginine (L-NMMA) (100 microM) or N(G)-nitro-L-arginine methyl ester (L-NAME) (200 microM) and with the guanylyl cyclase inhibitor methylene blue (100 microM). In addition, rutaecarpine (40-200 microM) did not significantly affect cyclic AMP and cyclic GMP levels in human washed platelets, whereas it significantly inhibited thromboxane B2 formation stimulated by collagen (10 microg/ml) and thrombin (0.1 U/ml). Furthermore, rutaecarpine (40-200 microM) inhibited [3H]inositol monophosphate formation stimulated by collagen and thrombin in [3H]myoinositol-loaded platelets. It is concluded that the antiplatelet effects of rutaecarpine are due to inhibition of thromboxane formation and phosphoinositide breakdown.
Sheu
J R
JR
Graduate Institute of Medical Sciences, Taipei Medical College, Taiwan.
Hung
W C
WC
Lee
Y M
YM
Yen
M H
MH
D000470:Alkaloids / Q000494:pharmacology*; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D006801:Humans; D026121:Indole Alkaloids; D009569:Nitric Oxide / Q000502:physiology; D010716:Phosphatidylinositols / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011799:Quinazolines; D013929:Thromboxane B2 / Q000096:biosynthesis; D052999:Quinazolinones
D000470:Alkaloids; D000242:Cyclic AMP; D006152:Cyclic GMP; D026121:Indole Alkaloids; D009569:Nitric Oxide; D010716:Phosphatidylinositols; D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; D013929:Thromboxane B2; C028632:rutecarpine; D052999:Quinazolinones