内皮素-1 介导的脑干胶质激活通过增强 ATP-P2X4 受体信号传导在 Sprague-Dawley 大鼠体内产生哮喘性气道迷走神经张力过高症

IF 5.2 3区 医学 Q1 NEUROSCIENCES
Yun Lin, Tian Liu, Hong Chen, Ming Zeng, Shunwei Hu, Xiaoning Yu, Yonghua Chen, Chunmei Xia, Jin Wang, Jijiang Wang
{"title":"内皮素-1 介导的脑干胶质激活通过增强 ATP-P2X4 受体信号传导在 Sprague-Dawley 大鼠体内产生哮喘性气道迷走神经张力过高症","authors":"Yun Lin, Tian Liu, Hong Chen, Ming Zeng, Shunwei Hu, Xiaoning Yu, Yonghua Chen, Chunmei Xia, Jin Wang, Jijiang Wang","doi":"10.1007/s11481-024-10116-y","DOIUrl":null,"url":null,"abstract":"<p>The occurrence of major asthma symptoms is largely attributed to airway vagal hypertonia, of which the central mechanisms remain unclear. This study tests the hypotheses that endothelin-1-mediated brainstem glial activation produces asthmatic airway vagal hypertonia via enhanced action of adenosine 5’-triphosphate on neuronal purinergic P2X4 receptors. A rat model of asthma was prepared using ovalbumin. Airway vagal tone was evaluated by the recurrent laryngeal discharge and plethysmographic measurement of pulmonary function. The changes in the brainstem were examined using ELISA, Western blot, luciferin-luciferase, quantitative reverse transcription-polymerase chain reaction, enzyme activity assay and immunofluorescent staining, respectively. The results showed that in the medulla of rats, endothelin receptor type B and P2X4 receptors were primarily expressed in astrocytes and neurons, respectively, and both of which, along with endothelin-1 content, were significantly increased after ovalbumin sensitization. Ovalbumin sensitization significantly increased recurrent laryngeal discharge, which was blocked by acute intracisternal injection of P2X4 receptor antagonist 5-BDBD, knockdown of brainstem P2X4 receptors, and chronic intraperitoneal injection of endothelin receptor type B antagonist BQ788, respectively. Ovalbumin sensitization activated microglia and astrocytes and significantly decreased ecto-5’-nucleotidase activity in the medulla, and all of which, together with the increase of medullary P2X4 receptor expression and decrease of pulmonary function, were reversed by chronic BQ788 treatment. These results demonstrated that in rats, allergic airway challenge activates both microglia and astrocytes in the medulla via enhanced endothelin-1/endothelin receptor type B signaling, which subsequently causes airway vagal hypertonia via augmented adenosine 5’-triphosphate/P2X4 receptor signaling in central neurons of airway vagal reflex.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\n","PeriodicalId":16500,"journal":{"name":"Journal of Neuroimmune Pharmacology","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Endothelin-1-mediated Brainstem Glial Activation Produces Asthmatic Airway Vagal Hypertonia Via Enhanced ATP-P2X4 Receptor Signaling in Sprague–Dawley Rats\",\"authors\":\"Yun Lin, Tian Liu, Hong Chen, Ming Zeng, Shunwei Hu, Xiaoning Yu, Yonghua Chen, Chunmei Xia, Jin Wang, Jijiang Wang\",\"doi\":\"10.1007/s11481-024-10116-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The occurrence of major asthma symptoms is largely attributed to airway vagal hypertonia, of which the central mechanisms remain unclear. This study tests the hypotheses that endothelin-1-mediated brainstem glial activation produces asthmatic airway vagal hypertonia via enhanced action of adenosine 5’-triphosphate on neuronal purinergic P2X4 receptors. A rat model of asthma was prepared using ovalbumin. Airway vagal tone was evaluated by the recurrent laryngeal discharge and plethysmographic measurement of pulmonary function. The changes in the brainstem were examined using ELISA, Western blot, luciferin-luciferase, quantitative reverse transcription-polymerase chain reaction, enzyme activity assay and immunofluorescent staining, respectively. The results showed that in the medulla of rats, endothelin receptor type B and P2X4 receptors were primarily expressed in astrocytes and neurons, respectively, and both of which, along with endothelin-1 content, were significantly increased after ovalbumin sensitization. Ovalbumin sensitization significantly increased recurrent laryngeal discharge, which was blocked by acute intracisternal injection of P2X4 receptor antagonist 5-BDBD, knockdown of brainstem P2X4 receptors, and chronic intraperitoneal injection of endothelin receptor type B antagonist BQ788, respectively. Ovalbumin sensitization activated microglia and astrocytes and significantly decreased ecto-5’-nucleotidase activity in the medulla, and all of which, together with the increase of medullary P2X4 receptor expression and decrease of pulmonary function, were reversed by chronic BQ788 treatment. These results demonstrated that in rats, allergic airway challenge activates both microglia and astrocytes in the medulla via enhanced endothelin-1/endothelin receptor type B signaling, which subsequently causes airway vagal hypertonia via augmented adenosine 5’-triphosphate/P2X4 receptor signaling in central neurons of airway vagal reflex.</p><h3 data-test=\\\"abstract-sub-heading\\\">Graphical Abstract</h3>\\n\",\"PeriodicalId\":16500,\"journal\":{\"name\":\"Journal of Neuroimmune Pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2024-04-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neuroimmune Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11481-024-10116-y\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neuroimmune Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11481-024-10116-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

摘要

哮喘主要症状的出现在很大程度上归因于气道迷走神经功能亢进,其中枢机制尚不清楚。本研究验证了内皮素-1 介导的脑干胶质细胞激活通过增强腺苷 5'-triphosphate 对神经元嘌呤能 P2X4 受体的作用产生哮喘气道迷走神经张力亢进的假设。使用卵清蛋白制备了大鼠哮喘模型。通过喉返神经放电和肺功能胸透测量评估了气道迷走神经张力。分别使用 ELISA、Western 印迹、荧光素-荧光素酶、定量反转录聚合酶链反应、酶活性测定和免疫荧光染色法检测了脑干的变化。结果表明,在大鼠髓质中,B型内皮素受体和P2X4受体主要分别在星形胶质细胞和神经元中表达,卵清蛋白致敏后,这两种受体和内皮素-1含量均显著增加。卵清蛋白致敏可显著增加喉部复发性放电,而急性胸腔内注射P2X4受体拮抗剂5-BDBD、敲除脑干P2X4受体和慢性腹腔内注射内皮素受体B型拮抗剂BQ788可分别阻断这种现象。卵清蛋白致敏激活了小胶质细胞和星形胶质细胞,并显著降低了髓质中外向-5'-核苷酸酶的活性,而所有这一切,连同髓质 P2X4 受体表达的增加和肺功能的降低,都被慢性 BQ788 治疗所逆转。这些结果表明,在大鼠体内,过敏性气道挑战通过增强内皮素-1/内皮素受体B型信号传导激活髓质中的小胶质细胞和星形胶质细胞,进而通过增强气道迷走神经反射中枢神经元的5'-三磷酸腺苷/P2X4受体信号传导引起气道迷走神经张力亢进。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Endothelin-1-mediated Brainstem Glial Activation Produces Asthmatic Airway Vagal Hypertonia Via Enhanced ATP-P2X4 Receptor Signaling in Sprague–Dawley Rats

Endothelin-1-mediated Brainstem Glial Activation Produces Asthmatic Airway Vagal Hypertonia Via Enhanced ATP-P2X4 Receptor Signaling in Sprague–Dawley Rats

The occurrence of major asthma symptoms is largely attributed to airway vagal hypertonia, of which the central mechanisms remain unclear. This study tests the hypotheses that endothelin-1-mediated brainstem glial activation produces asthmatic airway vagal hypertonia via enhanced action of adenosine 5’-triphosphate on neuronal purinergic P2X4 receptors. A rat model of asthma was prepared using ovalbumin. Airway vagal tone was evaluated by the recurrent laryngeal discharge and plethysmographic measurement of pulmonary function. The changes in the brainstem were examined using ELISA, Western blot, luciferin-luciferase, quantitative reverse transcription-polymerase chain reaction, enzyme activity assay and immunofluorescent staining, respectively. The results showed that in the medulla of rats, endothelin receptor type B and P2X4 receptors were primarily expressed in astrocytes and neurons, respectively, and both of which, along with endothelin-1 content, were significantly increased after ovalbumin sensitization. Ovalbumin sensitization significantly increased recurrent laryngeal discharge, which was blocked by acute intracisternal injection of P2X4 receptor antagonist 5-BDBD, knockdown of brainstem P2X4 receptors, and chronic intraperitoneal injection of endothelin receptor type B antagonist BQ788, respectively. Ovalbumin sensitization activated microglia and astrocytes and significantly decreased ecto-5’-nucleotidase activity in the medulla, and all of which, together with the increase of medullary P2X4 receptor expression and decrease of pulmonary function, were reversed by chronic BQ788 treatment. These results demonstrated that in rats, allergic airway challenge activates both microglia and astrocytes in the medulla via enhanced endothelin-1/endothelin receptor type B signaling, which subsequently causes airway vagal hypertonia via augmented adenosine 5’-triphosphate/P2X4 receptor signaling in central neurons of airway vagal reflex.

Graphical Abstract

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
13.60
自引率
0.00%
发文量
18
审稿时长
6-12 weeks
期刊介绍: The aims of the Journal of Neuroimmune Pharmacology are to promote the dissemination, interest, and exchange of new and important discoveries for the pharmacology and immunology of the nervous system. The aims parallel that of the Society on NeuroImmune Pharmacology by increasing the fundamental understanding of neurologic and neuropsychiatric disorders affected by the immune system or vice versa and towards pharmacologic measures that lead, either to a better understanding of disease mechanisms, or by improving disease outcomes. The scope of JNIP includes all primary works and reviews into the etiology, prevention, and treatment of neuroimmune and nervous system diseases affected by disordered immunity. Original studies serving to define neuroimmune modulation of environmental or endogenous cues such as toxins and drugs of abuse, hormones, and cytokines are welcome. JNIP will serve as a reliable source of interdisciplinary information bridging the fields of pharmacology, immunology, and neuroscience.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信