Kitagawa S, Ito Y, Oda Y, Kametani F
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Biochim Biophys Acta. 1989 Mar 28;1011(1):52-7. doi: 10.1016/0167-4889(89)90077-3.
The effects of phenol derivatives on aggregation of bovine platelets induced by ADP, thrombin, platelet activating factor, collagen and A23187 were investigated. The phenol derivatives inhibited all these induced aggregations except that by the calcium ionophore. The derivatives each inhibited the aggregations induced by ADP, thrombin, platelet activating factor and collagen, respectively, within a similar concentration range. A linear relation was found between the inhibitory potencies of the phenol derivatives and their partition coefficients between n-octanol and water (Poct values), suggesting that their interaction with hydrophobic regions of the cell was important for inhibition. Fluorescence analyses with fura-2-loaded platelets showed that in the concentration ranges in which the phenol derivatives inhibited aggregation, they also inhibited agonist-induced increases in Ca2+ both in the presence and absence of extracellular Ca2+. Moreover, a high correlation was found between the inhibitory effects of the derivatives on aggregation and their effects on Ca2+ mobilization. These results suggest that inhibition of platelet aggregation by phenol derivatives is mainly due to inhibition of the increase in cytoplasmic Ca2+ by inhibition of both intracellular Ca2+ mobilization and Ca2+ uptake.
研究了酚类衍生物对二磷酸腺苷（ADP）、凝血酶、血小板活化因子、胶原蛋白和A23187诱导的牛血小板聚集的影响。酚类衍生物抑制了所有这些诱导的聚集，但钙离子载体诱导的聚集除外。这些衍生物分别在相似的浓度范围内抑制ADP、凝血酶、血小板活化因子和胶原蛋白诱导的聚集。发现酚类衍生物的抑制效力与其在正辛醇和水之间的分配系数（Poct值）之间存在线性关系，这表明它们与细胞疏水区域的相互作用对于抑制作用很重要。用fura-2负载的血小板进行的荧光分析表明，在酚类衍生物抑制聚集的浓度范围内，无论细胞外有无钙离子，它们也抑制激动剂诱导的Ca2+增加。此外，发现衍生物对聚集的抑制作用与其对Ca2+动员的作用之间存在高度相关性。这些结果表明，酚类衍生物对血小板聚集的抑制主要是由于通过抑制细胞内Ca2+动员和Ca2+摄取来抑制细胞质Ca2+的增加。
