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蛋白磷酸酶抑制剂对人肺肥大细胞组胺释放及功能脱敏的作用

Role of protein phosphatases inhibitors on the histamine release and the functional desensitization in human lung mast cells.

作者信息

Bastan Reza, Eskandari Nahid, Sabzghabaee Ali Mohammad, Esfahani Seyyed Hamid Zarkesh, Peachell Peter T

机构信息

Department of Human Vaccines, Razi Serum and Vaccine Research Institute, Karaj, Iran.

Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

J Res Med Sci. 2014 Oct;19(10):923-7.

PMID:25538773
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4274566/
Abstract

BACKGROUND

The β2-adrenoceptor agonist, isoprenaline, is an effective inhibitor of histamine release from human lung mast cells (HLMC). Since phosphorylations of the β2-adrenoceptors are probably important in inducing desensitization, we sought to investigate the importance of phosphorylation events by targeting protein phosphatases (PPs) in mast cells. To this end, the effects of the inhibitor of on the functional desensitization of β-adrenoceptor-mediated responses in mast cells were investigated.

MATERIALS AND METHODS

In this study the effects of PP inhibitors on the inhibition of histamine release from HLMC, on β-agonists in mast cells and on desensitization were investigated.

RESULTS

Long-term exposure of mast cells to both isoprenaline and salbutamol substantially reduced the extent to which isoprenaline inhibited histamine release. Pretreatments of up to 24 h with inhibitors alone had no effect on immunoglobulin E-mediated histamine release. Shorter (≤4 h) pretreatments had little effect on the activity of isoprenaline and salbutamol to inhibit histamine release from mast cells.

CONCLUSION

Collectively, these data suggest that PP has an important role in regulating mast cell β2-adrenoceptors.

摘要

背景

β2肾上腺素能受体激动剂异丙肾上腺素是一种有效的抑制人肺肥大细胞(HLMC)释放组胺的物质。由于β2肾上腺素能受体的磷酸化可能在诱导脱敏中起重要作用,我们试图通过靶向肥大细胞中的蛋白磷酸酶(PPs)来研究磷酸化事件的重要性。为此,研究了该抑制剂对肥大细胞中β肾上腺素能受体介导反应的功能脱敏的影响。

材料与方法

在本研究中,研究了PP抑制剂对抑制HLMC释放组胺、对肥大细胞中β激动剂以及对脱敏的影响。

结果

肥大细胞长期暴露于异丙肾上腺素和沙丁胺醇会显著降低异丙肾上腺素抑制组胺释放的程度。单独用抑制剂预处理长达24小时对免疫球蛋白E介导的组胺释放没有影响。较短(≤4小时)的预处理对异丙肾上腺素和沙丁胺醇抑制肥大细胞释放组胺的活性影响很小。

结论

总体而言,这些数据表明PP在调节肥大细胞β2肾上腺素能受体中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3f5/4274566/e065d585a5d9/JRMS-19-923-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3f5/4274566/f2317f162dbb/JRMS-19-923-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3f5/4274566/1e57962892e3/JRMS-19-923-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3f5/4274566/e065d585a5d9/JRMS-19-923-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3f5/4274566/f2317f162dbb/JRMS-19-923-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3f5/4274566/1e57962892e3/JRMS-19-923-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3f5/4274566/e065d585a5d9/JRMS-19-923-g004.jpg

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本文引用的文献

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Characterization of isoprenaline- and salmeterol-stimulated interactions between beta2-adrenoceptors and beta-arrestin 2 using beta-galactosidase complementation in C2C12 cells.利用C2C12细胞中的β-半乳糖苷酶互补技术对异丙肾上腺素和沙美特罗刺激的β2-肾上腺素能受体与β-抑制蛋白2之间的相互作用进行表征。
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Protein kinase A and G protein-coupled receptor kinase phosphorylation mediates beta-1 adrenergic receptor endocytosis through different pathways.
蛋白激酶A和G蛋白偶联受体激酶磷酸化通过不同途径介导β-1肾上腺素能受体内吞作用。
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