Inhibition of mast cell mediator release by 5-amino-4-imidazolecarboxamide riboside.
Inhibition of mast cell mediator release by 5-amino-4-imidazolecarboxamide riboside.
复制标题
5-氨基-4-咪唑甲酰胺核苷抑制肥大细胞介质释放。
DOI：
10.1016/0006-2952(86)90757-4
复制
发表时间：
1986
影响因子：
5.8
通讯作者：
Gruber,HE
中科院分区：
文献类型：
--
作者：
Marquardt,DL;Gruber,HE
受刺激的肥大细胞产生并释放腺苷，并且肥大细胞介质的释放被腺苷增强，然而关于肥大细胞嘌呤代谢知之甚少。由于5-氨基-4-咪唑甲酰胺核苷（AICA核苷）已被证明可以改变腺苷代谢，加速其他组织中ATP库的补充，因此研究了其对肥大细胞功能的影响。无论是同时加入A23187和AICA核苷，还是与AICA核苷预孵育1小时，肥大细胞β-氨基己糖苷酶的释放都没有明显的改变。然而，在1-100 μM AICA核苷存在下培养2天或更长时间的小鼠骨髓源性肥大细胞与存在或不存在额外腺苷的对照细胞相比，对A23187的介质释放反应显著减弱。IgE介导的白三烯C4从AICA核苷暴露的肥大细胞产生更深刻的抑制，而不影响细胞活力或静息介质含量。先前在叶酸耗竭细胞中发现的一种不常见的三磷酸核糖核苷酸，5-氨基咪唑-4-甲酰胺-1-β-d-呋喃核糖基5′-三磷酸（ZTP），也在AICA核苷处理的肥大细胞中发现。虽然这种通过长期AICA核苷治疗全面抑制肥大细胞介质释放的机制尚不清楚，但肥大细胞嘌呤代谢的改变可能在过敏性疾病的治疗中被证明是重要的。
Stimulated mast cells produce and release adenosine, and the release of mast cell mediators is potentiated by adenosine, yet very little is known regarding mast cell purine metabolism. Because 5-amino-4-imidazolecarboxamide riboside (AICA riboside) has been shown to alter adenosine metabolism and accelerate the repletion of ATP pools in other tissues, its effects on mast cell function were examined. Neither simultaneous addition of A23187 and AICA riboside nor a 1-hr preincubation with AICA riboside altered mast cell β-hexosaminidase release to an appreciable degree. However, mouse bone marrow-derived mast cells cultured for 2 or more days in the presence of 1–100 μM AICA riboside exhibited a markedly attenuated mediator release response to A23187 compared to control cells with or without the additional presence of adenosine. IgE-mediated leukotriene C4generation from AICA riboside-exposed mast cells was even more profoundly inhibited without affecting cell viability or resting mediator content. An unusual ribonucleotide triphosphate previously identified in folate-depleted cells, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranosyl 5′-triphosphate (ZTP), has been identified in AICA riboside-treated mast cells as well. Although the mechanism of this global inhibition of mast cell mediator release by chronic AICA riboside treatment is not clear, alterations in mast cell purine metabolism may prove to be important in the treatment of allergic diseases.