Azuma H, Sekizaki S, Satoh A, Nakajima T
Proc Soc Exp Biol Med. 1986 May;182(1):34-42. doi: 10.3181/00379727-182-42305.
The pharmacological mechanisms of platelet aggregation induced by highly toxic proteins (CrTX-I, CrTX-II, and CrTX-III) obtained from tentacles of a jellyfish, Carybdea rastonii, were investigated. When the partially purified toxin (pCrTX) and CrTXs were added to the citrated platelet-rich plasma (PRP), aggregation was produced in a concentration-dependent manner. The activity of CrTXs was approximately 100 times more potent than pCrTX. The CrTXs-induced aggregation was little affected by indomethacin and quinacrine at concentrations sufficient to inhibit arachidonic acid- and collagen-induced aggregation. The CrTXs-induced aggregation in washed platelets was significantly augmented in the presence of Ca2+. The pretreatment with verapamil failed to modify this augmentation of aggregation. The concentration of cytoplasmic-free calcium ([Ca2+]i) of platelets was increased by CrTXs at the same concentrations that produced aggregation. This effect of CrTXs was again little affected by verapamil. CrTXs at the same concentrations as those that produced aggregation and increased [Ca2+]i caused depolarization of platelets, which was unchanged after pretreatment with sodium or potassium transport inhibitors. CrTX-I significantly increased the 22Na flux into platelets and this effect of CrTX-I was unaffected by tetrodotoxin. The CrTX-I-induced aggregation, depolarization, and increase in [Ca2+]i were all significantly attenuated in the low Na+ medium. These results suggest that CrTXs cause a massive depolarization by increasing cation permeability and this generalized depolarization permits an inward movement of Ca2+ down its electrochemical gradient which, in turn, triggers platelet aggregation.
研究了从僧帽水母触手获取的高毒性蛋白（CrTX-I、CrTX-II和CrTX-III）诱导血小板聚集的药理机制。当将部分纯化的毒素（pCrTX）和CrTX添加到枸橼酸化富血小板血浆（PRP）中时，会以浓度依赖的方式产生聚集。CrTX的活性比pCrTX强约100倍。在足以抑制花生四烯酸和胶原诱导的聚集的浓度下，吲哚美辛和喹吖因对CrTX诱导的聚集影响很小。在Ca2+存在的情况下，洗涤血小板中CrTX诱导的聚集显著增强。用维拉帕米预处理未能改变这种聚集增强。在产生聚集的相同浓度下，CrTX会使血小板的胞质游离钙浓度（[Ca2+]i）升高。CrTX的这种作用同样很少受到维拉帕米的影响。与产生聚集的浓度相同的CrTX会导致血小板去极化，在用钠或钾转运抑制剂预处理后，这种去极化没有变化。CrTX-I显著增加22Na流入血小板，并且CrTX-I的这种作用不受河豚毒素的影响。在低钠培养基中，CrTX-I诱导的聚集、去极化和[Ca2+]i升高均显著减弱。这些结果表明，CrTX通过增加阳离子通透性导致大量去极化，这种普遍的去极化允许Ca2+沿其电化学梯度向内移动，进而触发血小板聚集。
