ADP-mimicking platelet aggregation caused by rugosin E, an ellagitannin isolated from Rosa rugosa Thunb.
Among the nine ellagitannins, rugosin E was the most potent platelet aggregating agent with an EC50 of 1.5 +/- 0.1 microM in rabbit platelets and 3.2 +/- 0.1 microM in human platelets. The aggregations caused by rugosin E and ADP were inhibited by EGTA, PGE1, mepacrine, sodium nitroprusside and neomycin, but not by indomethacin, verapamil, TMB-8, BN52021 and GR32191B. Rugosin E-induced thromboxane formation was suppressed by indomethacin, EGTA, PGE1, verapamil, mepacrine, TMB-8 and neomycin. ADP-scavenging agents, such as CP/CPK and apyrase inhibited concentration-dependently ADP (20 microM)-, but not rugosin E (5 microM)-induced platelet aggregation. In thrombin (0.1 U/ml)-treated and degranulated platelets, rugosin E and ADP still caused 63.5 +/- 3.0% and 61.2 +/- 3.5% of platelet aggregation, respectively. Selective ADP receptor antagonists, ATP and FSBA inhibited rugosin E- and ADP-induced platelet aggregations in a concentration-dependent manner. Both rugosin E and ADP did not induce platelet aggregation in ADP (1 mM)-desensitized platelets. In contrast to ADP, rugosin E did not decrease cAMP formation in washed rabbit platelets. Both rugosin E and ADP did not cause phosphoinositide breakdown in [3H]myo-inositol-labeled rabbit platelets. In fura-2/AM-load platelets, both rugosin E and ADP induced increase in intracellular calcium concentration and these responses were inhibited by ATP and PGE1. All these data suggest that rugosin E may be an ADP receptor agonist in rabbit platelets.
Teng
C M
CM
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Kang
Y F
YF
Chang
Y L
YL
Ko
F N
FN
Yang
S C
SC
Hsu
F L
FL
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000345:Affinity Labels / Q000378:metabolism; D000818:Animals; D001081:Apyrase / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000097:blood; D003402:Creatine Kinase / Q000378:metabolism; D006801:Humans; D047348:Hydrolyzable Tannins; D007295:Inositol Phosphates / Q000097:blood; D010725:Phosphocreatine / Q000494:pharmacology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011817:Rabbits; D013634:Tannins / Q000302:isolation & purification / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood
D000345:Affinity Labels; D047348:Hydrolyzable Tannins; D007295:Inositol Phosphates; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D013634:Tannins; C013515:ellagitannin; D010725:Phosphocreatine; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; C010959:5'-(4-fluorosulfonylbenzoyl)adenosine; C106155:rugosin E; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D001081:Apyrase; D000241:Adenosine; D002118:Calcium