Engels F, Folkerts G, van Heuven-Nolsen D, Nijkamp F P
Institute for Veterinary Pharmacology, Pharmacy, and Toxicology, Department of Pharmacology, Faculty of Veterinary Sciences, Utrecht, The Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 1987 Sep;336(3):274-9. doi: 10.1007/BF00172678.
In the guinea-pig intraperitoneal administration of the Gram-negative bacterium Haemophilus influenzae induces a decrease of beta-adrenoceptor number and results in impairment of beta-adrenoceptor function in the peripheral and central airways, respectively. In the present study, the time-course of these events was studied and compared with changes in catecholamines in plasma, in organs involved in immunoregulation (spleen, thymus), and in the heart and the lung. The number of beta-adrenoceptor binding sites in peripheral lung tissue and beta-adrenoceptor function in isolated tracheal spirals were significantly decreased 3 and 4 days after administration of H. influenzae (24-33%). No significant changes were observed at day 1 and day 8. The effects on tracheal beta-adrenergic receptor function were characterized by a decrease of maximal relaxation only, whereas EC50-values were not affected. These data are indicative of an effect on the functional coupling of the receptors to the biochemical events leading to smooth muscle relaxation. No changes were observed in catecholamine concentrations in the lung, heart, and the thymus after H. influenzae-treatment. Plasma noradrenaline, though, was significantly increased at day 1 after H. influenzae. At day 8 plasma noradrenaline had returned to control levels. Interestingly, the effect on spleen noradrenaline was opposite to the effect seen in plasma. A significant decrease in spleen noradrenaline was observed after H. influenzae at days 1, 3, and 8, with a maximum of 42% at day 1. It is suggested that the decrease in spleen noradrenaline may have a causal relationship with the changes in lung beta-adrenoceptors.
在豚鼠中，腹腔注射革兰氏阴性菌流感嗜血杆菌会导致β-肾上腺素能受体数量减少，并分别导致外周和中央气道的β-肾上腺素能受体功能受损。在本研究中，对这些事件的时间进程进行了研究，并与血浆、参与免疫调节的器官（脾脏、胸腺）以及心脏和肺中的儿茶酚胺变化进行了比较。流感嗜血杆菌给药后3天和4天，外周肺组织中β-肾上腺素能受体结合位点的数量以及离体气管螺旋条中的β-肾上腺素能受体功能显著降低（24%-33%）。在第1天和第8天未观察到显著变化。对气管β-肾上腺素能受体功能的影响仅表现为最大舒张度降低，而半数有效浓度（EC50）值不受影响。这些数据表明对受体与导致平滑肌舒张的生化事件的功能偶联有影响。流感嗜血杆菌处理后，肺、心脏和胸腺中的儿茶酚胺浓度未观察到变化。然而，流感嗜血杆菌给药后第1天血浆去甲肾上腺素显著升高。在第8天，血浆去甲肾上腺素已恢复到对照水平。有趣的是，对脾脏去甲肾上腺素的影响与血浆中的影响相反。流感嗜血杆菌给药后第1天、第3天和第8天观察到脾脏去甲肾上腺素显著降低，第1天最大降幅为42%。有人认为脾脏去甲肾上腺素的降低可能与肺β-肾上腺素能受体的变化存在因果关系。
