Ribbi-Jaffe A, Apitz-Castro R
Biochem J. 1979 Feb 15;178(2):449-54. doi: 10.1042/bj1780449.
The effects of colchicine on ADP-induced aggregation and on the phosphorylation of tubulin-like protein from human blood platelets were studied. Colchicine at 2mM concentration completely inhibits ADP-induced aggregation after 8min incubation. Under the same inhibitory conditions, phosphorylation of tubulin-like materials in intact platelets was also impaired whereas the endogenous kinase activity of tubulin, isolated through polymerization--depolymerization cycles, was not affected. It was also shown that, under conditions of maximal inhibition of both aggregation and tubulin phosphorylation, colchicine does not penetrate into the cells. The results obtained suggest that the effect of colchicine on platelet aggregation might be mainly, although not exclusively, due to a non-specific effect of the alkaloid on the plasma membrane, rather than to a direct action of the drug on the microtubular protein subunits.
研究了秋水仙碱对人血小板中ADP诱导的聚集以及微管蛋白样蛋白磷酸化的影响。2mM浓度的秋水仙碱在孵育8分钟后完全抑制ADP诱导的聚集。在相同的抑制条件下,完整血小板中微管蛋白样物质的磷酸化也受到损害,而通过聚合-解聚循环分离的微管蛋白的内源性激酶活性不受影响。还表明,在聚集和微管蛋白磷酸化均受到最大抑制的条件下,秋水仙碱不会进入细胞。所得结果表明,秋水仙碱对血小板聚集的作用可能主要(尽管不是唯一)是由于生物碱对质膜的非特异性作用,而不是药物对微管蛋白亚基的直接作用。