Kadota H, Kuwahara M, Nishibata R, Mikami H, Tsubone H
Department of Comparative Pathophysiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Exp Anim. 2001 Jan;50(1):49-58. doi: 10.1538/expanim.50.49.
The expression balance of M2 and M3 muscarinic receptor subtypes on the pathogenesis of airway hyperresponsiveness was investigated by using two congenitally related strains of guinea pigs, bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR). CCh-induced airway responses in vivo and in vitro were investigated by comparing the effects of muscarinic receptor subtype antagonists, and the relative amounts of M2 and M3 muscarinic receptor mRNA in tracheal smooth muscle and lung tissue were investigated. After treatment with muscarinic receptor subtype antagonists, the ventilatory mechanics (VT, Raw, and Cdyn) of response to CCh aerosol inhalation were measured by the bodyplethysmograph method. The effects of these antagonists on CCh-induced tracheal smooth muscle contraction were also investigated. The effects of M2 muscarinic receptor blockade were less but the effects of M3 muscarinic receptors blockade on the airway contractile responses were greater in BHS than in BHR. In M3 muscarinic receptor blockades, CCh-induced tracheal contractions in BHS were significantly greater than those in BHR. In tracheal smooth muscle from BHS, the relative amount of M2 muscarinic receptors mRNA was less but that of M3 muscarinic receptor mRNA was more than those in BHR. These results suggest that the high ACh level as a consequence of dysfunction of M2 muscarinic autoreceptors and the excessive effect of M3 muscarinic receptors on the airway smooth muscle may play an important role in the pathogenesis of airway hyperresponsiveness.
通过使用两种先天性相关的豚鼠品系，即支气管高敏（BHS）和支气管低敏（BHR）品系，研究了M2和M3毒蕈碱受体亚型的表达平衡在气道高反应性发病机制中的作用。通过比较毒蕈碱受体亚型拮抗剂的作用，研究了体内和体外CCh诱导的气道反应，并研究了气管平滑肌和肺组织中M2和M3毒蕈碱受体mRNA的相对含量。在用毒蕈碱受体亚型拮抗剂治疗后，通过体容积描记法测量对CCh气雾剂吸入反应的通气力学（VT、Raw和Cdyn）。还研究了这些拮抗剂对CCh诱导的气管平滑肌收缩的作用。M2毒蕈碱受体阻断的作用较小，但M3毒蕈碱受体阻断对气道收缩反应的作用在BHS中比在BHR中更大。在M3毒蕈碱受体阻断中，CCh诱导的BHS气管收缩明显大于BHR中的收缩。在BHS的气管平滑肌中，M2毒蕈碱受体mRNA的相对含量低于BHR，而M3毒蕈碱受体mRNA的相对含量高于BHR。这些结果表明，M2毒蕈碱自身受体功能障碍导致的高ACh水平以及M3毒蕈碱受体对气道平滑肌的过度作用可能在气道高反应性的发病机制中起重要作用。
