Teng C M, Kang Y F, Chang Y L, Ko F N, Yang S C, Hsu F L
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Thromb Haemost. 1997 Mar;77(3):555-61.
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.
在九种鞣花单宁中，rugosin E是最有效的血小板聚集剂，在兔血小板中的EC50为1.5±0.1微摩尔，在人血小板中的EC50为3.2±0.1微摩尔。EGTA、PGE1、米帕林、硝普钠和新霉素可抑制rugosin E和ADP引起的聚集，但吲哚美辛、维拉帕米、TMB - 8、BN52021和GR32191B则不能。吲哚美辛、EGTA、PGE1、维拉帕米、米帕林、TMB - 8和新霉素可抑制rugosin E诱导的血栓素形成。ADP清除剂，如CP/CPK和腺苷三磷酸双磷酸酶可浓度依赖性地抑制ADP（20微摩尔）诱导的血小板聚集，但不能抑制rugosin E（5微摩尔）诱导的血小板聚集。在凝血酶（0.1 U/ml）处理和脱颗粒的血小板中，rugosin E和ADP仍分别引起63.5±3.0%和61.2±3.5%的血小板聚集。选择性ADP受体拮抗剂ATP和FSBA可浓度依赖性地抑制rugosin E和ADP诱导的血小板聚集。rugosin E和ADP在ADP（1 mM）脱敏的血小板中均不诱导血小板聚集。与ADP不同，rugosin E不会降低洗涤过的兔血小板中的cAMP形成。rugosin E和ADP在[3H]肌醇标记的兔血小板中均不会引起磷酸肌醇分解。在fura - 2/AM负载的血小板中，rugosin E和ADP均诱导细胞内钙浓度升高，且这些反应可被ATP和PGE1抑制。所有这些数据表明，rugosin E可能是兔血小板中的一种ADP受体激动剂。
