ATP-induced histamine release is in part related to phospholipase A2-mediated arachidonic acid metabolism in rat peritoneal mast cells
ATP-induced histamine release is in part related to phospholipase A2-mediated arachidonic acid metabolism in rat peritoneal mast cells
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DOI：
10.1007/bf02975164
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发表时间：
2001-12-01
影响因子：
6.7
通讯作者：
Sim, SS
中科院分区：
文献类型：
--
作者：
Lee, YH;Lee, SJ;Sim, SS
用P2-嘌呤受体拮抗剂磷脂酶A（2）（PLA（2））和环氧合酶（考克斯）/脂氧合酶（LOX）抑制剂测定大鼠腹腔肥大细胞组胺和花生四烯酸（AA）的释放，以确定ATP诱导的组胺释放是否与花生四烯酸（AA）的释放有关。ATP以剂量依赖性方式增加组胺释放，而腺苷没有。PPADS（选择性P2 X嘌呤受体拮抗剂）和苏拉明（非选择性P2 X，2 Y嘌呤受体拮抗剂）以剂量依赖方式抑制ATP诱导的组胺释放。然而，RB-2（P2 Y-嘌呤受体拮抗剂）并不阻断ATP诱导的组胺释放。Manoalide和oleyloxyethyl phosphorylcholine（OPC）是PLA（2）的分泌型抑制剂，也能剂量依赖性地抑制ATP诱导的组胺释放。考克斯抑制剂（布洛芬和吲哚美辛）和LOX抑制剂（黄芩素和咖啡酸）以剂量依赖性方式抑制ATP诱导的组胺。ATP显著增加[H-3]AA释放54%。PRADS和苏拉明显著抑制ATP诱导的[H-3]AA释放，分别为81%和39%。多种蛋白激酶抑制剂，如双吲哚马来酰亚胺，染料木素，甲基2，5-二羟基肉桂酸，W-7和三氟拉嗪显着抑制ATP诱导的组胺释放。总之，结果表明ATP诱导的组胺释放部分与PLA（2）介导的AA代谢和P2 X-嘌呤受体有关。
Histamine and arachidonic acid (AA) release was measured using the P2-purinoceptor antagonists, phospholipase A(2) (PLA(2)) and cyclooxygenase (COX)/lipoxygenase (LOX) inhibitors to determine whether or not ATP-induced histamine release is associated with arachidonic acid (AA) release in rat peritoneal mast cells. ATP increased histamine release in a dose dependent manner, whereas adenosine did not. PPADS (a selective P2X-purinoceptor antagonist) and suramin (a nonselective P2X,2Y-purinoceptor antagonist) inhibited ATP-induced histamine release in a dose dependent manner. However, RB-2 (a P2Y-purinoceptor antagonist) did not block ATP-induced histamine release. Manoalide and oleyloxyethyl phosphorylcholine (OPC), secretory PLA(2) inhibitors, also inhibited ATP-induced histamine release dose-dependently. Both COX inhibitors (ibuprofen and indomethacin) and LOX inhibitors (baicalein and caffeic acid) inhibited ATP-induced histamine in a dose dependent manner. ATP significantly increased [H-3]AA release by 54%. PRADS and suramin significantly inhibited ATP-induced [H-3]AA release by 81% and 39%, respectively. ATP-induced histamine release was significantly inhibited by a variety of protein kinase inhibitors, such as bisindolmaleimide, genistein, methyl 2,5-dihydroxycinnamate, W-7 and trifluoperazine. Overall, the results suggest that ATP-induced histamine release is in part related to the PLA(2)-mediated AA metabolism and P2X-purinoceptors.