Modulation of mast cell responses to adenosine by agents that alter protein kinase C activity.
Modulation of mast cell responses to adenosine by agents that alter protein kinase C activity.
复制标题
通过改变蛋白激酶 C 活性的药物调节肥大细胞对腺苷的反应。
DOI：
10.1016/0006-2952(90)90611-n
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发表时间：
1990
影响因子：
5.8
通讯作者：
Walker,LL
中科院分区：
文献类型：
--
作者：
Marquardt,DL;Walker,LL
小鼠骨髓来源的肥大细胞与已知激活蛋白激酶C的低浓度试剂[佛波醇肉豆蔻酸酯(PMA)、1，2-二辛酰甘油(DIC8)和1-油酰基-2-乙酰甘油(OAG)]急性孵育后，可促进钙离子载体A23187刺激的β-己糖胺酶释放。较高浓度的蛋白激酶C激活剂倾向于抑制A23187或抗原诱导的预形成介质的释放。所研究的所有浓度均可诱导肥大细胞对腺苷的介质释放增强效应产生明显的低反应性。已报道的阻断蛋白激酶C活性的药物[1-(5-isoquinolinesulfonyl)-2-methylpiperazine二盐酸盐(H-7)和鞘氨醇]在这个系统中表现出不同的反应。在存在或不存在PMA和促分泌剂的情况下，高达100μ的M H-7不能影响肥大细胞β-己糖苷酶的释放。鞘氨醇(10μM)是抗原或A23187诱导的介质释放和腺苷反应性的有效抑制剂。鞘氨醇还以剂量依赖的方式阻断了上述PMA的作用。令人惊讶的是，受刺激的肥大细胞产生白三烯C4(LTC4)没有受到显著抑制颗粒相关介质释放的diC8浓度的影响。在用A23187、单独腺苷和DiC8在泰氏缓冲液、A23187或腺苷存在的情况下短暂处理的细胞中，蛋白激酶C活性明显地从胞浆转移到肥大细胞膜。这些发现进一步支持了从肥大细胞腺苷受体到调节脱颗粒过程的信号转导可能涉及蛋白激酶C的观点。
The acute incubation of mouse bone marrow-derived mast cells with low concentrations of agents known to activate protein kinase C [phorbol myristate acetate (PMA), 1,2-dioctanoyl-sn-glycerol (diC8), and 1-oleoyl-2-acetyl-glycerol (OAG)] caused an enhancement of β-hexosaminidase release stimulated by the calcium ionophore A23187. Higher concentrations of protein kinase C activators tended to inhibit A23187- or antigen-induced preformed mediator release. All concentrations studied induced a striking mast cell hyporesponsiveness to the mediator release augmenting effect of adenosine. Agents that have been reported to block protein kinase C activity [1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and sphingosine] demonstrated diverse responses in this system. Up to 100 μM H-7 failed to affect mast cell β-hexosaminidase release in the presence or absence of PMA and secretagogue. Sphingosine (10 μM) was a potent inhibitor of antigen- or A23187-induced mediator release as well as adenosine responsiveness. Sphingosine also blocked the effects of PMA noted above in a dose-dependent fashion. The generation of leukotriene C4(LTC4) by stimulated mast cells surprisingly was not affected by concentrations of diC8 that significantly inhibited granule-associated mediator release. Translocation of protein kinase C activity from the cytosol to the mast cell membrane was evident in cells briefly pretreated with A23187, adenosine alone, and diC8 in the presence of Tyrode's buffer, A23187, or adenosine. These findings lend further support to the contention that signal transduction from mast cell adenosine receptors to processes that regulate degranulation may involve protein kinase C.