Alteration of mast cell responsiveness to adenosine by pertussis toxin.
Alteration of mast cell responsiveness to adenosine by pertussis toxin.
复制标题
百日咳毒素改变肥大细胞对腺苷的反应性。
DOI：
10.1016/0006-2952(88)90088-3
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发表时间：
1988
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
腺苷通过一种似乎涉及细胞表面腺苷受体的机制促进小鼠骨髓来源的肥大细胞介质的释放。为了探索G蛋白和腺苷受体之间可能的相互作用，在用特定抗原或钙离子载体A23187攻击肥大细胞之前，将肥大细胞与激活的百日咳毒素孵育，激活的百日咳毒素是一种ADP核糖化并灭活某些G蛋白亚型的试剂。用10ngml百日咳毒素预育肥大细胞至少2小时，可抑制抗原诱导的β-氨基己糖苷酶和白三烯C4的释放。百日咳毒素对腺苷促进β-己糖苷酶释放的能力有更大程度的减弱。A23187刺激的介质释放不受百日咳毒素的影响，尽管在经百日咳毒素处理的肥大细胞中观察到腺苷对A23187诱导的β-氨基己糖苷酶的释放有轻微的抑制作用。尽管长达24小时暴露于100 ng毫升百日咳毒素不会改变静息状态下肥大细胞的环磷酸腺苷水平，但当毒素剂量高于影响介质释放所需的剂量时，腺苷升高细胞环磷酸腺苷浓度的能力明显减弱。百日咳毒素治疗既不改变抗原刺激的细胞内游离钙水平的升高，也不改变腺苷对这些水平的额外增强。在IgE介导的机制刺激下，肥大细胞产生三磷酸肌醇，但百日咳毒素预先孵育不影响其产生。综上所述，腺苷似乎在肥大细胞生化事件中通过一种被百日咳毒素部分抑制的机制产生了一些变化。与肥大细胞腺苷受体相关的G蛋白的性质尚未确定。
Adenosine potentiates mouse bone marrow-derived mast cell mediator release by a mechanism that appears to involve cell surface adenosine receptors. In an attempt to explore possible interactions between G proteins and adenosine receptors, mast cells were incubated with activated pertussis toxin, an agent that ADP-ribosylates and inactivates some G protein subtypes, prior to challenge with specific antigen or the calcium ionophore A23187. Mast cells preincubated with 10 ng ml pertussis toxin for at least 2hr exhibited an inhibition of antigen-induced β-hexosaminidase and leukotriene C 4 release. The ability of adenosine to potentiate β-hexosaminidase release was attenuated to an even greater degree by pertussis toxin. A23187-stimulated mediator release was not altered by pertussis toxin, although a modest inhibition of the ability of adenosine to enhance A23187-induced β-hexosaminidase release was observed in pertussis toxin-treated mast cells. Although up to 24-hr exposure to 100 ng ml pertussis toxin did not alter resting mast cell cyclic AMP levels, the ability of adenosine to elevate cell cyclic AMP concentrations was diminished markedly by doses of the toxin higher than those required to affect mediator release. Neither antigen-stimulated intracellular free calcium level augmentation alone nor the additional potentiation of these levels by adenosine was changed by pertussis toxin treatment. Inositol trisphosphate was generated by mast cells stimulated by IgE-mediated mechanisms, but a preincubation with pertussis toxin did not influence its generation. In summary, adenosine appeared to produce some of its alterations in mast cell biochemical events by a mechanism that was partially inhibited by pertussis toxin. The nature of the G protein linked to the mast cell adenosine receptor is yet to be determined.