Belmonte K E, Fryer A D, Costello R W
Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins Asthma and Allergy Center, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
J Appl Physiol (1985). 1998 Nov;85(5):1708-18. doi: 10.1152/jappl.1998.85.5.1708.
In the lungs, neuronal M2 muscarinic receptors limit ACh release from parasympathetic nerves. In antigen-challenged animals, eosinophil proteins block these receptors, resulting in increased ACh release and vagally mediated hyperresponsiveness. In contrast, diabetic rats are hyporesponsive and have increased M2 receptor function. Because there is a low incidence of asthma among diabetic patients, we investigated whether diabetes protects neuronal M2 receptor function in antigen-challenged rats. Antigen challenge of sensitized rats decreased M2 receptor function, increased vagally mediated hyperreactivity by 75%, and caused a 10-fold increase in eosinophil accumulation around airway nerves. In antigen-challenged diabetic rats, neuronal M2 receptor function was preserved and there was no eosinophil accumulation around airway nerves. Insulin treatment of diabetic rats completely restored loss of M2 receptor function, vagally mediated hyperresponsiveness, and eosinophilia after antigen challenge. These data demonstrate that insulin is required for development of airway inflammation, loss of neuronal M2 muscarinic receptor function, and subsequent hyperresponsiveness in antigen-challenged rats and may explain decreased incidence of asthma among diabetic humans.
在肺部，神经元M2毒蕈碱受体限制乙酰胆碱从副交感神经释放。在抗原激发的动物中，嗜酸性粒细胞蛋白会阻断这些受体，导致乙酰胆碱释放增加以及迷走神经介导的高反应性。相比之下，糖尿病大鼠反应低下且M2受体功能增强。由于糖尿病患者中哮喘发病率较低，我们研究了糖尿病是否能保护抗原激发大鼠的神经元M2受体功能。对致敏大鼠进行抗原激发会降低M2受体功能，使迷走神经介导的高反应性增加75%，并导致气道神经周围嗜酸性粒细胞积聚增加10倍。在抗原激发的糖尿病大鼠中，神经元M2受体功能得以保留，气道神经周围没有嗜酸性粒细胞积聚。用胰岛素治疗糖尿病大鼠可完全恢复抗原激发后M2受体功能丧失、迷走神经介导的高反应性以及嗜酸性粒细胞增多的情况。这些数据表明，胰岛素是抗原激发大鼠气道炎症发展、神经元M2毒蕈碱受体功能丧失以及随后高反应性所必需的，这可能解释了糖尿病患者中哮喘发病率降低的原因。
