Bowerfind William M L, Fryer Allison D, Jacoby David B
Division of Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
J Appl Physiol (1985). 2002 Apr;92(4):1417-22. doi: 10.1152/japplphysiol.00934.2001.
Viral infection causes dysfunction of inhibitory M2 muscarinic receptors (M2Rs) on parasympathetic nerves, leading to airway hyperreactivity. The mechanisms of M2R dysfunction are incompletely understood. Double-stranded RNA (dsRNA), a product of viral replication, promotes the expression of interferons. Interferon-gamma decreases M2R gene expression in cultured airway parasympathetic neurons. In this study, guinea pigs were treated with dsRNA (1 mg/kg ip) on 2 consecutive days. Twenty-four hours later, anesthetized guinea pigs had dysfunctional M2Rs and were hyperresponsive to electrical stimulation of the vagus nerves, in the absence of inflammation. DsRNA did not affect either cholinesterase or the function of postjunctional M3 muscarinic receptors on smooth muscle. M2Rs on the nerves supplying the heart were also dysfunctional, but M2Rs on the heart muscle itself functioned normally. Thus dsRNA causes increased bronchoconstriction and bradycardia via increased release of ACh from the vagus nerves because of loss of M2R function on parasympathetic nerves in the lungs and heart. Production of dsRNA may be a mechanism by which viruses cause dysfunction of neuronal M2Rs and airway hyperreactivity.
病毒感染导致副交感神经上的抑制性M2毒蕈碱受体（M2Rs）功能障碍，从而引起气道高反应性。M2R功能障碍的机制尚未完全明确。双链RNA（dsRNA）是病毒复制的产物，可促进干扰素的表达。γ干扰素可降低培养的气道副交感神经元中M2R基因的表达。在本研究中，连续两天给豚鼠腹腔注射dsRNA（1mg/kg）。24小时后，麻醉的豚鼠出现M2R功能障碍，并且在无炎症的情况下对迷走神经的电刺激反应性增强。dsRNA对胆碱酯酶或平滑肌上的节后M3毒蕈碱受体功能均无影响。供应心脏的神经上的M2Rs也功能异常，但心肌本身的M2Rs功能正常。因此，由于肺和心脏副交感神经上M2R功能丧失，dsRNA通过增加迷走神经释放乙酰胆碱（ACh）导致支气管收缩增强和心动过缓。dsRNA的产生可能是病毒导致神经元M2R功能障碍和气道高反应性的一种机制。
