Inhibition of collagen-induced platelet aggregation and adhesion by a pseudocyanide derivative of avicine isolated from Zanthoxylum integrifoliolum Merr.
Avicine pseudocyanide, a derivative of avicine isolated from Zanthoxylum integrifoliolum Merr., inhibited collagen-induced platelet aggregation and release reaction in a concentration-dependent manner. Trimucytin is a collagen-like snake venom protein isolated from Trimeresurus mucrosquamatus. Avicine pseudocyanide also inhibited trimucytin (1 microgram/mL)-induced platelet aggregation and release reaction concentration dependently. The IC50 values of avicine pseudocyanide on collagen (10 micrograms/mL)- and trimucytin (1 microgram/mL)-induced platelet aggregation were 47.3 +/- 4.1 and 62.5 +/- 5.6 microM, respectively. Avicine pseudocyanide at a concentration of 300 microM inhibited less than 30% of platelet aggregation induced by ADP (20 microM), AA (100 microM), U46619 (1 microM), PAF (2 ng/mL) and thrombin (0.1 U/mL). The concentration-response curve of collagen-induced platelet aggregation was shifted to the right by avicine pseudocyanide (20-100 microM) concentration dependently. The Schild plot showed that pA2 and pA10 values of avicine pseudocyanide were 4.8 and 4.3, respectively, with slope of -1.9. Avicine pseudocyanide also inhibited collagen (10 micrograms/mL)-induced aggregation of rabbit whole blood with an IC50 of 145 +/- 13 microM. Collagen-induced thromboxane B2 formation was also inhibited by avicine pseudocyanide in a concentration-dependent manner with a maximal effect at 100 microM. However, arachidonic acid (AA)-induced thromboxane B2 and prostaglandin D2 formations were only partially suppressed by a high concentration of avicine pseudocyanide (300 microM). Avicine pseudocyanide (100 microM) inhibited the [3H]inositol monophosphate formation and the rise of intracellular Ca2+ concentration caused by collagen but not those caused by AA, U46619, platelet-activating factor and thrombin. In the presence of prostaglandin E1, Mg(2+)-dependent platelet adhesion to collagen was inhibited by avicine pseudocyanide with an IC50 of 278 +/- 16 microM. These data indicate that avicine pseudocyanide is an inhibitor of collagen-induced platelet aggregation and platelet-collagen adhesion.
Ko
F N
FN
Pharmacological Institute, College of Medicine, National Taiwan University, Tapei.
Hsiao
G
G
Chen
I S
IS
Wu
S J
SJ
Teng
C M
CM
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D003094:Collagen / Q000037:antagonists & inhibitors*; D004149:Dioxoles / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal; D007295:Inositol Phosphates / Q000096:biosynthesis; D010617:Phenanthridines / Q000737:chemistry / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000096:biosynthesis; D011509:Proteoglycans / Q000494:pharmacology; D011817:Rabbits; D013329:Structure-Activity Relationship; D013929:Thromboxane B2 / Q000096:biosynthesis
D004149:Dioxoles; D004365:Drugs, Chinese Herbal; D007295:Inositol Phosphates; D010617:Phenanthridines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011509:Proteoglycans; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; C026064:aggregoserpentin; D000255:Adenosine Triphosphate; D003094:Collagen; C083790:avicine pseudocyanide; D015230:Prostaglandin D2; D002118:Calcium