Sweatt J D, Schwartzberg M S, Frazer M, Cragoe E J, Blair I A, Reed P W, Limbird L E
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232.
Circ Res. 1987 Nov;61(5 Pt 2):II6-11.
We have found previously that inhibitors of Na+-H+ exchange block platelet arachidonic acid release and subsequent secondary aggregation and serotonin release in response to epinephrine, ADP, and thrombin (0.004 U/ml). The present study demonstrates that the addition of ethylisopropylamiloride, an inhibitor of Na+-H+ exchange, leads to an inhibition of platelet activating factor-induced serotonin release and thromboxane B2 production in human platelets in citrated plasma. In addition, platelet activating factor-induced platelet secretion is blocked by the cyclooxygenase inhibitor indomethacin or the thromboxane antagonist SQ 29548, indicating that arachidonic acid mobilization and metabolism is required for platelet activating factor to elicit platelet activation. Our interpretation of the present findings is that platelet activating factor-induced secretion of dense granules from the human platelet requires the production of cyclooxygenase metabolites from arachidonic acid and that Na+-H+ exchange plays an important, albeit not exclusive, role in mobilization of arachidonic acid in response to platelet activating factor.
我们之前发现，钠氢交换抑制剂可阻断血小板花生四烯酸的释放以及随后因肾上腺素、二磷酸腺苷（ADP）和凝血酶（0.004 U/ml）而引发的继发性聚集和5-羟色胺释放。本研究表明，添加钠氢交换抑制剂乙基异丙基amiloride可抑制枸橼酸盐血浆中人类血小板的血小板激活因子诱导的5-羟色胺释放和血栓素B2生成。此外，血小板激活因子诱导的血小板分泌被环氧化酶抑制剂吲哚美辛或血栓素拮抗剂SQ 29548阻断，这表明花生四烯酸的动员和代谢是血小板激活因子引发血小板激活所必需的。我们对目前这些发现的解释是，血小板激活因子诱导人类血小板致密颗粒的分泌需要从花生四烯酸生成环氧化酶代谢产物，并且钠氢交换在响应血小板激活因子时花生四烯酸的动员中起重要作用，尽管不是唯一作用。
