长春碱对人血小板中丙二醛形成、5-羟色胺释放及聚集的影响。

Effects of vinblastine on malondialdehyde formation, serotonin release and aggregation in human platelets.

作者信息

Brammer J P, Kerecsen L, Maguire M H

出版信息

Eur J Pharmacol. 1982 Jul 30;81(4):577-85. doi: 10.1016/0014-2999(82)90347-8.

Abstract

Effects of the microtubular agent vinblastine on human platelet malondialdehyde formation, [14C]serotonin release and aggregation were studied in suspensions of [14C]serotonin-labelled platelets. Vinblastine caused dose-dependent inhibition of malondialdehyde formation and aggregation in platelet suspensions stimulated with thrombin, ADP or palmitaldehyde acetal phosphatidic acid (PGAP). Malondialdehyde formation, aggregation and [14C]serotonin release caused by threshold doses of thrombin were reduced but not abolished by 100 muM vinblastine; 30-100 muM vinblastine abolished ADP- and PGAP-induced malondialdehyde formation and [14C]serotonin released and transformed ADP- and PGAP-induced irreversible aggregation to a diminished reversible response. Arachidonate conversion to malondialdehyde catalysed by human platelet microsomes was inhibited by vinblastine and the cyclooxygenase inhibitors indomethacin and aspirin, but not by salicylate. Vinblastine inhibited the microsome-catalysed formation of malondialdehyde from prostaglandin H2. It is concluded that vinblastine inhibits the thromboxane pathway of arachidonate metabolism in stimulated platelets, consequently inhibiting release and aggregation, and that this effect of vinblastine may be, at least in part, independent of its antimicrotubular actions.

摘要

在[14C]5-羟色胺标记的血小板悬液中，研究了微管药物长春碱对人血小板丙二醛形成、[14C]5-羟色胺释放及聚集的影响。长春碱对由凝血酶、二磷酸腺苷（ADP）或棕榈醛缩醛磷脂酸（PGAP）刺激的血小板悬液中的丙二醛形成及聚集产生剂量依赖性抑制作用。100μM长春碱可使凝血酶阈剂量引起的丙二醛形成、聚集及[14C]5-羟色胺释放减少，但未完全消除；30 - 100μM长春碱可消除ADP和PGAP诱导的丙二醛形成及[14C]5-羟色胺释放，并使ADP和PGAP诱导的不可逆聚集转变为减弱的可逆反应。长春碱以及环氧化酶抑制剂吲哚美辛和阿司匹林均可抑制人血小板微粒体催化的花生四烯酸向丙二醛的转化，但水杨酸盐无此作用。长春碱抑制微粒体催化的前列腺素H2转化为丙二醛。结论是长春碱抑制受刺激血小板中花生四烯酸代谢的血栓素途径，从而抑制释放及聚集，且长春碱的这种作用可能至少部分独立于其抗微管作用。