Mehta P N, Panitch H B, Wolfson M R, Shaffer T H
Department of Physiology, Temple University School of Medicine, Philadelphia PA 19140.
Pediatr Res. 1991 May;29(5):446-8. doi: 10.1203/00006450-199105010-00007.
Xanthine derivatives relax adult airway smooth muscle (ASM). To determine whether caffeine and theophylline relax preterm ASM contracted by acetylcholine, 27 tracheal rings obtained from seven preterm lambs (120-135 d gestation) were studied. ASM was contracted using 10(-5) M acetylcholine (control) after the muscle was stretched to the length at which maximum active tension was developed isometrically. Concentration-effect curves for each xanthine were obtained by cumulative addition of the drug. Theophylline produced a significant decrease (p less than 0.001) in active tension at each dose, whereas caffeine significantly increased (p less than 0.001) active tension at 10(-4) and 10(-3) M concentrations. Addition of caffeine and theophylline to previously uncontracted ASM did not alter tension. Thus, it appears that, in contrast to their effect on adult ASM, the xanthine derivatives caffeine and theophylline have differential effects on prestimulated ASM in preterm lambs. These findings raise important questions about various aspects of the current therapeutic use of caffeine and theophylline.
黄嘌呤衍生物可舒张成年气道平滑肌（ASM）。为了确定咖啡因和茶碱是否能舒张由乙酰胆碱收缩的早产期ASM，对从7只早产羔羊（妊娠120 - 135天）获取的27个气管环进行了研究。在肌肉被拉伸至等长产生最大主动张力的长度后，使用10⁻⁵ M乙酰胆碱（对照）使ASM收缩。通过逐次添加药物获得每种黄嘌呤的浓度 - 效应曲线。茶碱在每个剂量下均使主动张力显著降低（p < 0.001），而咖啡因在10⁻⁴和10⁻³ M浓度时显著增加（p < 0.001）主动张力。将咖啡因和茶碱添加到先前未收缩的ASM中不会改变张力。因此，与它们对成年ASM的作用相反，黄嘌呤衍生物咖啡因和茶碱对早产羔羊中预先刺激的ASM具有不同的作用。这些发现引发了关于咖啡因和茶碱当前治疗用途各个方面的重要问题。
