Gardier R W, Blaxall H S, Killian L N, Cunningham J
Department of Pharmacology, Wright State University, School of Medicine, Dayton, Ohio 45435.
Life Sci. 1991;48(18):1705-13. doi: 10.1016/0024-3205(91)90206-q.
Radioligand binding was conducted on airways of the rat and human, surgically subdivided into trachea, lung airways, and parenchyma. 3H-QNB bound uniformly to receptors in separate sections of the rat and human airway. Receptor densities generally were ranked: lung airways greater than trachea greater than parenchyma. Receptor subtypes were identified mostly by pirenzepine displacement of bound 3H-QNB. The rat trachea, and rat and human lung airways had a uniformly low affinity for pirenzepine while rat and human parenchyma demonstrated both high and low affinity pirenzepine binding. Inhibition of methacholine-stimulated smooth muscle contraction by the M1 receptor antagonist, pirenzepine, and M2 receptor antagonist, gallamine, was studied in rat trachea and bronchus in vitro. Schild plot pA2 values were compatible with low potency antagonism, thereby favoring the presence of M3 receptors at these smooth muscle sites. Reserpine treatment of rats (0.5 mg kg-1 day-1 for 7 days) produced a decrease in peak tension in response to methacholine without changing the muscarinic receptor character (Kd 3H-QNB), population density (Bmax in fmol mg-1 protein), or function (methacholine EC50). These results indicate that muscarinic receptor heterogeneity exists in the airway of both laboratory rat and man. While the muscarinic receptor subserving airway smooth muscle contraction appears to be the M3 subtype, decreased contractile responses to methacholine by trachea and bronchus from reserpine-treated rats were receptor independent.
放射性配体结合实验在大鼠和人类的气道上进行，这些气道通过手术被细分为气管、肺气道和实质组织。³H-QNB 均匀地结合在大鼠和人类气道的不同节段中的受体上。受体密度通常的排序为：肺气道大于气管大于实质组织。受体亚型主要通过哌仑西平对结合的³H-QNB 的置换来确定。大鼠气管以及大鼠和人类的肺气道对哌仑西平的亲和力均较低，而大鼠和人类的实质组织则表现出对哌仑西平的高亲和力和低亲和力结合。在体外对大鼠气管和支气管中，研究了 M1 受体拮抗剂哌仑西平和 M2 受体拮抗剂加拉明对乙酰甲胆碱刺激的平滑肌收缩的抑制作用。Schild 图的 pA2 值与低效拮抗作用相符，因此支持在这些平滑肌部位存在 M3 受体。用利血平（0.5 mg kg⁻¹ 每天，共 7 天）处理大鼠，会使对乙酰甲胆碱的反应峰值张力降低，但不会改变毒蕈碱受体特性（³H-QNB 的 Kd）、群体密度（以 fmol mg⁻¹ 蛋白质计的 Bmax）或功能（乙酰甲胆碱的 EC50）。这些结果表明，实验室大鼠和人类的气道中均存在毒蕈碱受体异质性。虽然参与气道平滑肌收缩的毒蕈碱受体似乎是 M3 亚型，但利血平处理的大鼠的气管和支气管对乙酰甲胆碱的收缩反应降低与受体无关。
