Bruner G, Murphy S
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City.
J Neurochem. 1990 Nov;55(5):1569-75. doi: 10.1111/j.1471-4159.1990.tb04940.x.
To reveal more of the mechanism whereby ATP induces arachidonic acid (AA) mobilization in astrocytes, primary cell cultures prelabeled with [3H]AA were exposed to ATP and various analogs. Release of 3H was dose and time dependent and was inhibited by blocking ATP binding. The potencies of a range of ATP analogs in mobilizing AA were consistent with that predicted for the involvement of a P2Y-purinergic receptor. Mobilization of AA was not due to non-specific cell permeabilization, as assessed by leakage of cytoplasmic lactate dehydrogenase. AA mobilization by ATP was reduced when mobilization of intracellular calcium was inhibited and in the absence of extracellular calcium. Thapsigargin, which induces release of intracellular calcium, evoked mobilization of AA and thromboxane formation, findings similar to the effects of ATP. These results suggest that ATP stimulates AA mobilization via a P2Y-purinergic receptor and that, although extracellular calcium is involved, mobilization of intracellular calcium activates phospholipase A2.
为了更深入地揭示ATP诱导星形胶质细胞中花生四烯酸（AA）释放的机制，将预先用[3H]AA标记的原代细胞培养物暴露于ATP及各种类似物中。3H的释放呈剂量和时间依赖性，并可通过阻断ATP结合而受到抑制。一系列ATP类似物在动员AA方面的效力与P2Y嘌呤能受体参与所预测的情况一致。通过细胞质乳酸脱氢酶的泄漏评估，AA的动员并非由于非特异性的细胞通透性增加。当细胞内钙的动员受到抑制以及细胞外无钙时，ATP诱导的AA动员减少。毒胡萝卜素可诱导细胞内钙的释放，它能引起AA的动员和血栓素的形成，这一结果与ATP的作用相似。这些结果表明，ATP通过P2Y嘌呤能受体刺激AA的动员，并且尽管细胞外钙参与其中，但细胞内钙的动员激活了磷脂酶A2。
