McKay R T, Brooks S M
Am Rev Respir Dis. 1983 Jul;128(1):50-3. doi: 10.1164/arrd.1983.128.1.50.
The effects of toluene diisocyanate (TDI) on beta adrenergic receptor function was investigated using 2 different experimental model systems: (1) a biochemical model measured beta adrenergic adenylate cyclase activity of frog erythrocytes and (2) guinea pig tracheal smooth muscle responsiveness after in vivo exposure was used to assess physiologic function. The TDI inhibited isoproterenol-stimulated erythrocyte adenylate cyclase activity in a dose-dependent manner. Similar results were obtained with fluoride-ion-stimulated activity, suggesting that TDI caused a nonspecific inhibition of adenylate cyclase activity. No difference in tracheal smooth muscle responsiveness, measured as the concentration of isoproterenol corresponding to 50% of maximal relaxation (ED50), was observed in TDI-exposed (9.36 +/- 0.11 SE) guinea pigs when compared with control (9.38 +/- 0.06 SE) animals, nor was there a difference in the degree of maximal relaxation induced by isoproterenol. The differences between the in vitro cell studies and the tracheal smooth muscle investigations suggest that mechanisms other than direct beta adrenergic blockade should be considered in TDI-induced asthma.
使用两种不同的实验模型系统研究了甲苯二异氰酸酯（TDI）对β肾上腺素能受体功能的影响：（1）一种生化模型，测量青蛙红细胞的β肾上腺素能腺苷酸环化酶活性；（2）体内暴露后豚鼠气管平滑肌反应性，用于评估生理功能。TDI以剂量依赖的方式抑制异丙肾上腺素刺激的红细胞腺苷酸环化酶活性。氟离子刺激的活性也得到了类似结果，表明TDI对腺苷酸环化酶活性产生了非特异性抑制。与对照（9.38±0.06 SE）动物相比，在暴露于TDI的（9.36±0.11 SE）豚鼠中，未观察到气管平滑肌反应性的差异，以对应于最大舒张50%的异丙肾上腺素浓度（ED50）来衡量，异丙肾上腺素诱导的最大舒张程度也没有差异。体外细胞研究与气管平滑肌研究之间的差异表明，在TDI诱发的哮喘中，应考虑除直接β肾上腺素能阻断以外的机制。
