Kanesa-thasan N, Douglas J G, Kazura J W
Case Western Reserve University, Department of Pediatrics, OH.
Mol Biochem Parasitol. 1991 Nov;49(1):11-9. doi: 10.1016/0166-6851(91)90125-p.
Diethylcarbamazine (DEC) rapidly lowers the number of microfilariae in the peripheral circulation. The mechanism of action is unknown, but may involve alterations of arachidonic acid metabolism in vascular tissues. We studied the effects of DEC on arachidonic acid metabolism by bovine pulmonary arterial endothelium monolayers, human platelets and Brugia malayi microfilariae. DEC at a concentration of 2.5 microM, a level achieved in vivo, rapidly decreased prostacyclin, prostaglandin E2 and thromboxane B2 release from endothelial monolayers by 78% (P less than 0.001), 57% (P = 0.05), and 75% (P less than 0.05), respectively. High-pressure liquid chromatography of extracts of endothelial monolayers incubated with DEC showed similar inhibition of these cyclooxygenase pathway products, but exposure to the drug did not result in formation of new eicosanoids. DEC did not inhibit endothelial phospholipase A2-dependent release of arachidonate from membrane stores, whereas prostaglandin H2 synthase activity (cyclooxygenae, EC 1.14.99.1) was reduced to a degree similar to that effected by acetylsalicylic acid. Microfilarial but not platelet synthesis of cyclooxygenase products was also reduced by DEC. These data suggest that the mechanism by which DEC lowers the level of microfilariae in the circulation may in part involve its effects on host endothelial and parasite eicosanoid production.
乙胺嗪（DEC）能迅速降低外周循环中微丝蚴的数量。其作用机制尚不清楚，但可能涉及血管组织中花生四烯酸代谢的改变。我们研究了DEC对牛肺动脉内皮单层细胞、人血小板和马来布鲁线虫微丝蚴花生四烯酸代谢的影响。体内可达到的浓度为2.5微摩尔的DEC，能使内皮单层细胞中前列环素、前列腺素E2和血栓素B2的释放分别迅速减少78%（P<0.001）、57%（P=0.05）和75%（P<0.05）。对与DEC一起孵育的内皮单层细胞提取物进行高压液相色谱分析，显示对这些环氧化酶途径产物有类似的抑制作用，但接触该药物并未导致新的类花生酸形成。DEC并不抑制内皮磷脂酶A2介导的花生四烯酸从膜储存库中的释放，而前列腺素H2合酶活性（环氧化酶，EC 1.14.99.1）降低的程度与乙酰水杨酸所造成的程度相似。DEC还降低了微丝蚴而非血小板中环氧化酶产物的合成。这些数据表明，DEC降低循环中微丝蚴水平的机制可能部分涉及其对宿主内皮细胞和寄生虫类花生酸生成的影响。
