Effect of docosahexaenoic acid (DHA) on arachidonic acid metabolism and platelet function.
Effect of docosahexaenoic acid (DHA) on arachidonic acid metabolism and platelet function.
复制标题
二十二碳六烯酸（DHA）对花生四烯酸代谢和血小板功能的影响。
DOI：
10.1016/0006-291x(83)91235-4
复制
发表时间：
1983
影响因子：
3.1
通讯作者：
White,JG
中科院分区：
文献类型：
--
作者：
Rao,GH;Radha,E;White,JG
我们实验室的研究表明亚铁在花生四烯酸代谢中的作用，并证明前列腺素合成抑制剂通过与环氧合酶的血红素基团络合而发挥作用。二十二碳六烯酸（DHA）是绵羊泡腺前列腺素合成酶代谢花生四烯酸的强竞争性抑制剂。在这项研究中，我们评估了外源性添加DHA对血小板功能和花生四烯酸代谢的影响。150 μM浓度的DHA抑制血小板对450 μM花生四烯酸的聚集。在此浓度下，DHA还抑制血小板对肾上腺素、二磷酸腺苷和凝血酶等激动剂作用的第二波反应。这种脂肪酸诱导的抑制作用可被较高浓度的激动剂克服。DHA抑制标记的花生四烯酸转化为血栓素的完整，洗涤血小板悬浮液。然而，首先用DHA孵育，然后用标记的花生四烯酸盐洗涤和搅拌的血浆中的血小板产生与对照血小板一样多的血栓烷。这些结果表明，多烯酸，如果在环氧合酶附近释放足够的量，可以有效地竞争血红素位点，并抑制花生四烯酸的转化。
Studies from our laboratory have suggested a role for ferrous iron in the metabolism of arachidonic acid and demonstrated that inhibitors of prostaglandin synthesis exert their effect by complexing with the heme group of cyclooxygenase. Docosahexaenoic acid (DHA) is a potent competitive inhibitor of arachidonic acid metabolism by sheep vesicular gland prostaglandin synthetase. In this study we have evaluated the effect of exogenously added DHA on platelet function and arachidonic acid metabolism. DHA at 150 μM concentration inhibited aggregation of platelets to 450 μM arachidonic acid. At this concentration DHA also inhibited the second wave of the platelet response to the action of agonists such as epinephrine, adenosine diphosphate and thrombin. Inhibition induced by this fatty acid could be overcome by the agonists at higher concentrations. DHA inhibited the conversion of labeled arachidonic acid to thromboxane by intact, washed platelet suspensions. However, platelets in plasma incubated first with DHA then washed and stirred with labeled arachidonate generated as much thromboxane as control platelets. These results suggest that the polyenoic acids, if released in sufficient quantities in the vicinity of cyclooxygenase, could effectively compete for the heme site and inhibit the conversion of arachidonic acid.