Böhm M, Gengenbach S, Hauck R W, Sunder-Plassmann L, Erdmann E
Medizinische Klinik I, University of Munich, Germany.
Chest. 1991 Nov;100(5):1246-53. doi: 10.1378/chest.100.5.1246.
In order to investigate whether treatment with terbutaline (1 mg subcutaneously) in patients with bronchial obstruction is accompanied by changes in the densities of receptors of the autonomic nervous system, beta-adrenergic receptors or m-cholinergic receptors were measured in membrance preparations of human peripheral lung tissue from patients undergoing lung resection for bronchial carcinoma. The density of beta-adrenergic receptors and mononuclear leukocytes (MNLs) of treated and untreated patients and beta-adrenergic receptors and m-cholinergic receptors in lung strips from the same patients exposed to terbutaline in vitro were studied for comparison. In patients, treatment with terbutaline did not have any effect on human lung beta-adrenergic receptors and m-cholinergic receptors, whereas a 57 percent decline was measured in the number of beta-receptors on MNLs of the very same patients. In contrast, in vitro exposure of human peripheral lung strips to terbutaline (100 mumol/L for 36 hours) evoked a time-dependent and concentration-dependent decline of 46 percent in beta-adrenergic receptors. Again, there was no change in the number of m-cholinergic receptors. The antagonist affinities, as judged from the KD values, did not differ under either condition. We concluded that lung beta-adrenergic receptors are subject to down-regulation when exposed to agonists in vitro. This down-regulation in the human lung is not accompanied by alterations in m-cholinergic receptors. Down-regulation of beta-adrenergic receptors or up-regulation of m-cholinergic receptors appears not to play a role in the proposed tolerance to beta-adrenergic receptor agonist treatment in clinical situations. The reduction of beta-adrenergic receptors in MNLs provides evidence that treatment with terbutaline was sufficient to affect beta-adrenergic receptors in vivo in certain cell types but also shows that alterations in blood cells do not necessarily reflect the situation in the lung.
为了研究支气管阻塞患者皮下注射特布他林（1毫克）治疗后自主神经系统受体密度是否发生变化，我们在因支气管癌接受肺切除术患者的人外周肺组织膜制剂中测量了β - 肾上腺素能受体或M胆碱能受体。研究了治疗组和未治疗组患者的β - 肾上腺素能受体密度及单核白细胞（MNLs），并比较了同一患者的肺条在体外暴露于特布他林后的β - 肾上腺素能受体和M胆碱能受体情况。在患者中，特布他林治疗对人肺β - 肾上腺素能受体和M胆碱能受体没有任何影响，而同一患者的MNLs上β受体数量下降了57%。相比之下，人外周肺条在体外暴露于特布他林（100微摩尔/升，36小时）后，β - 肾上腺素能受体出现了时间和浓度依赖性下降，降幅为46%。同样，M胆碱能受体数量没有变化。根据解离常数（KD）值判断，两种情况下拮抗剂亲和力没有差异。我们得出结论，肺β - 肾上腺素能受体在体外暴露于激动剂时会发生下调。人肺中的这种下调并不伴有M胆碱能受体的改变。β - 肾上腺素能受体下调或M胆碱能受体上调似乎在临床情况下对β - 肾上腺素能受体激动剂治疗的耐受性中不起作用。MNLs中β - 肾上腺素能受体的减少证明特布他林治疗足以在体内影响某些细胞类型中的β - 肾上腺素能受体，但也表明血细胞的变化不一定反映肺中的情况。
