Jeppsson A B, Sundler F, Luts A, Waldeck B, Widmark E
Research and Development Department, AB Draco Lund, Sweden.
Pulm Pharmacol. 1991;4(2):73-9. doi: 10.1016/0952-0600(91)90055-8.
An isolated vagus nerve-tracheal tube preparation from guinea-pig was treated intraluminally with hydrogen peroxide (H2O2) at various concentrations. Exposure to, 100 mmol/L H2O2 for 20 min was chosen for further experiments since it appeared to cause selective damage to the epithelium. Thus the subepithelial layers of the tracheal wall appeared intact as judged by light microscopic examination. The response to nerve stimulation (increase in intratracheal pressure) was attenuated by only about 20%. Terbutaline administration into the tracheal lumen caused a concentration-dependent inhibition of the response to nerve stimulation. In tracheal preparations pretreated with 100 mmol/L H2O2 there was a 20-fold decrease in the EC50 for terbutaline. The EC50 for terbutaline added to the external medium was not changed by the H2O2 pretreatment. The efflux of 3H-terbutaline from the tracheal lumen into the external medium was three times higher in H2O2-treated than in control preparations. It is concluded that in the H2O2-damaged epithelium the absorption of terbutaline is enhanced resulting in a better availability of the drug in the smooth muscle layer after intraluminal administration.
将豚鼠的离体迷走神经 - 气管插管标本管腔内用不同浓度的过氧化氢（H₂O₂）处理。由于100 mmol/L H₂O₂暴露20分钟似乎会对上皮造成选择性损伤，因此选择该处理条件用于进一步实验。通过光学显微镜检查判断，气管壁的上皮下层似乎完好无损。神经刺激引起的反应（气管内压升高）仅减弱约20%。向气管腔内给予特布他林会引起对神经刺激反应的浓度依赖性抑制。在用100 mmol/L H₂O₂预处理的气管标本中，特布他林的半数有效浓度（EC₅₀）降低了20倍。添加到外部介质中的特布他林的EC₅₀不受H₂O₂预处理的影响。经H₂O₂处理的气管标本中，³H - 特布他林从气管腔向外部介质的流出量是对照标本的三倍。得出的结论是，在H₂O₂损伤的上皮中，特布他林的吸收增强，导致腔内给药后药物在平滑肌层中的可用性更好。
