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Studies on mechanisms of development of airway hyperresponsiveness in rat bronchial asthma

支气管哮喘大鼠气道高反应性发生机制的研究

基本信息

批准号：
07672392
负责人：
MISAWA Miwa
金额：
$ 1.34万
依托单位：
Hoshi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672392/
关键词：
bronchial asthma airway hyperresponsiveness muscarinic receptors G protein Ca^<2+> channel neurokinins beta-receptors 気道過敏性気管支平滑筋 sensory neuropeptide ACh受容体 neutral endopeptidase Ca availability

项目摘要

The mechanisms of airway hyperresponsiveness (AHR) which lays behind bronchial asthma were investigated with rat allergy-induced AHR model developed by us. The following results were obtained.1. Affinity of high affinity agonist binding sites of muscarinic receptor on bronchus was remarkably enhanced in AHR rats. The high affinity seemed to be linked to an increase in G protein level.2. The bronchial constriction induced by cumulative administration of Ca^<2+> when preincubated with ACh under Ca^<2+>-free condition was significantly greater in AHR bronchus than in normal one. This suggests that availability of Ca^<2+> that liberates from sarcoplasmic reticulum and/or influxes into cells through receptor-operated Ca^<2+> channel is augmented in AHR.3. The neutral endopeptidase (NEP) activity of AHR bronchus was decreased, and NEP inhibitors themselves enhanced the ACh-induced bronchial constriction. It is therefore suggested that neurokinins accumulation in bronchial tissues evokes an incrased ACh release from cholinergic nerve endings through NK_2 receptors which leadsto AHR.4. Taking consideration of the results on receptor binding assays, the function and number of beta-receptors in bronchial tissues are unaltered in AHR,which denies the involvement of down-regulation of beta-receptors in the development of AHR.

本研究采用大鼠过敏性气道高反应性（AHR）模型，探讨支气管哮喘的气道高反应性机制。得到以下结果. AHR大鼠支气管M受体高亲和力激动剂结合位点的亲和力明显增强。高亲和力似乎与G蛋白水平的增加有关。在无Ca^<2 +>条件下，ACh预孵育AHR支气管，累积Ca^<2 +>引起的支气管收缩作用显著大于正常支气管。这表明AHR中从肌浆网释放和/或通过受体操纵的Ca^<2+>通道流入细胞的Ca^<2 +>的可用性增加。AHR支气管中性内肽酶（NEP）活性降低，NEP抑制剂本身增强ACh引起的支气管收缩。提示支气管组织中神经激肽的蓄积通过NK_2受体引起胆碱能神经末梢释放ACh增加，从而引起AHR.考虑到受体结合试验的结果，支气管组织中β受体的功能和数量在AHR中没有改变，这否认了β受体的下调参与AHR的发展。