Guillot C, Fornaris M, Badier M, Orehek J
J Allergy Clin Immunol. 1984 Nov;74(5):713-8. doi: 10.1016/0091-6749(84)90235-5.
Cumulative concentration-response curves to isoproterenol were constructed in 74 preparations of human airways (group A) contracted with acetylcholine (80% of maximal contraction). In 52 bronchi (group A1), the maximal relaxation to isoproterenol represented at least 70% of the acetylcholine contraction (average 98% +/- 3) and the mean concentration (+/- SD) causing 50% of the relaxation (EC50) was 6.0 X 10(-8)M +/- 0.8. Resistance to isoproterenol (significant decrease of the maximal relaxation and right shift of the concentration-response curve) was provoked in 25 preparations by incubating them with isoproterenol (concentration 100 times higher than the individual EC50) for 30 min. The response to isoproterenol remained stable over the same time interval in eight control preparations. Incubation with isoproterenol did not modify the relaxing response to theophylline (n = 8). Indomethacin had no effect on the resistance provoked by isoproterenol incubation (n = 11). Incomplete relaxation to isoproterenol (maximal relaxation averaging 47% +/- 2 of the acetylcholine contraction) was observed in 22 preparations (group A2; mean EC50 = 1 X 10(-6)M +/- 0.2, significantly different [p less than 0.001] from group A1). Such preparations could be completely relaxed by theophylline (n = 7). For the whole group A, a significant negative correlation was found between isoproterenol EC50 and the magnitude of the maximal relaxation to isoproterenol (expressed as percent of acetylcholine contraction). There was no significant correlation between acetylcholine EC50 and isoproterenol maximum relaxation. Spontaneous resistance to isoproterenol was neither related to the technique of isoproterenol administration (cumulative versus noncumulative; n = 11) nor the magnitude of acetylcholine contraction (70% and 95% of maximal contraction; 14 bronchi, group B).
在74份用乙酰胆碱收缩（达最大收缩的80%）的人呼吸道标本（A组）中构建了对异丙肾上腺素的累积浓度 - 反应曲线。在52条支气管（A1组）中，对异丙肾上腺素的最大舒张至少占乙酰胆碱收缩的70%（平均98%±3），引起50%舒张的平均浓度（±标准差）（EC50）为6.0×10⁻⁸M±0.8。通过将25份标本与异丙肾上腺素（浓度比个体EC50高100倍）孵育30分钟，引发了对异丙肾上腺素的抵抗（最大舒张显著降低且浓度 - 反应曲线右移）。在8份对照标本中，对异丙肾上腺素的反应在相同时间间隔内保持稳定。与异丙肾上腺素孵育未改变对茶碱的舒张反应（n = 8）。吲哚美辛对异丙肾上腺素孵育引发的抵抗无影响（n = 11）。在22份标本（A2组）中观察到对异丙肾上腺素的不完全舒张（最大舒张平均为乙酰胆碱收缩的47%±2）；平均EC50 = 1×10⁻⁶M±0.2，与A1组有显著差异（p < 0.001）。此类标本可被茶碱完全舒张（n = 7）。对于整个A组，发现异丙肾上腺素EC50与对异丙肾上腺素的最大舒张幅度（以乙酰胆碱收缩的百分比表示）之间存在显著负相关。乙酰胆碱EC50与异丙肾上腺素最大舒张之间无显著相关性。对异丙肾上腺素的自发抵抗既与异丙肾上腺素给药技术（累积与非累积；n = 11）无关，也与乙酰胆碱收缩幅度（最大收缩的70%和95%；14条支气管，B组）无关。
