Function of pulmonary neuronal M2 muscarinic receptors in stable chronic obstructive pulmonary disease
Function of pulmonary neuronal M2 muscarinic receptors in stable chronic obstructive pulmonary disease
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DOI：
10.1164/ajrccm.163.6.2002129
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发表时间：
2001-05-01
影响因子：
24.7
通讯作者：
Costello, RW
中科院分区：
文献类型：
--
作者：
On, LS;Boonyoncsunchai, P;Costello, RW
抗胆碱能药物通常会导致慢性阻塞性肺病（COPD）患者出现相当程度的支气管扩张。肺神经元 M-2 毒蕈碱受体的功能是限制迷走神经诱导的支气管收缩的幅度。我们假设抗胆碱能药物对 COPD 患者的有效性可能反映了由于 M-2 毒蕈碱受体功能障碍导致迷走神经反应性增加。在肺功能正常的受试者和患有 COPD 的受试者中评估了 M-2 受体的功能和迷走神经诱导的支气管收缩的程度。使用鼻冷干燥空气挑战来诱导支气管收缩，使用脉冲振荡法测量 5 Hz (R5) 下气道阻力 (Raw) 的变化。在患有慢性阻塞性肺病的受试者中，在冷干燥空气挑战后，R5 从 0.68 +/- 0.06 上升到 0.74 +/- 0.07 kPa/L/s (p < 0.01)，而在对照受试者中，R5 从 0.34 0.03 上升到 0.39 +/- 0.03 kPa/L/s (p < 0.01)。用异丙托溴铵预处理可抑制支气管收缩，表明它是迷走神经介导的。在两组受试者中，用选择性 M-2 毒蕈碱受体激动剂毛果芸香碱 (5 mg/ml) 进行预处理可防止冷空气引起的支气管收缩，表明 M-2 受体功能正常。这些研究表明 M-2 毒蕈碱受体在稳定型 COPD 受试者中发挥功能。
Anticholinergic drugs often cause a considerable degree of bronchodilation in patients with chronic obstructive pulmonary disease (COPD). Pulmonary neuronal M-2 muscarinic receptors function to limit the magnitude of vagally induced bronchoconstriction. We hypothesized that the effectiveness of anticholinergic agents in patients with COPD may reflect increased vagal reactivity due to dysfunction of M-2 muscarinic receptors. The function of M-2 receptors and the magnitude of vagally induced bronchoconstriction were assessed in subjects with normal lung function and in subjects with COPD. A nasal cold dry air challenge was used to induce a bronchoconstriction, measured as a change in airway resistance (Raw) at 5 Hz (R5) using impulse oscillometry. In subjects with COPD R5 rose from 0.68 +/- 0.06 to 0.74 +/- 0.07 kPa/L/s after the cold dry air challenge (p < 0.01) and in the control subjects R5 rose from 0.34 0.03 to 0.39 +/- 0.03 kPa/L/s (p < 0.01). The bronchoconstriction was inhibited by pretreatment with ipratropium bromide, indicating that it was vagally mediated. In both groups of subjects pretreatment with the selective M-2 muscarinic receptor agonist pilocarpine (5 mg/ml) prevented the cold air-induced bronchoconstriction, indicating normal function of M-2 receptors. These studies indicate that M-2 muscarinic receptors are functional in subjects with stable COPD.