Titinchi S, Al Shamma M, Patel K R, Kerr J W, Clark B
Clin Sci (Lond). 1984 Mar;66(3):323-8. doi: 10.1042/cs0660323.
To determine whether circadian variation in adrenoceptor function might underlie the 'morning dip' in peak expiratory flow (PEF) rate and its abolition by salbutamol we measured indices of beta-adrenoceptor function (Bmax. and Kd), the ratio FEV1/FVC, and plasma cortisol at 08.00 and 18.00 hours on and off salbutamol (4 mg given orally every 4 h) in five extrinsic asthmatic patients and five normal volunteers. There was a significant circadian variation in receptor numbers (Bmax.) in both the control and asthmatic groups which was not abolished on treatment with salbutamol. Both groups appeared to compensate for loss of receptor number induced by salbutamol administration by increasing receptor affinity. For comparable combinations of drug/time, there was no significant difference between the control and asthmatic groups. We conclude that the 'morning dip' observed in asthmatic patients cannot simply be explained by changes in cell receptor number or affinity, as our results suggest that both groups have intact beta-adrenoceptor function. Nevertheless, our observations of the normal circadian rhythm has important implications for future studies of beta-adrenoceptors in asthmatic patients.
为了确定肾上腺素能受体功能的昼夜变化是否可能是呼气峰值流速（PEF）“晨降”现象及其被沙丁胺醇消除的潜在原因，我们在5名外源性哮喘患者和5名正常志愿者中，于08:00和18:00时测量了服用和未服用沙丁胺醇（每4小时口服4毫克）时的β - 肾上腺素能受体功能指标（最大结合容量Bmax和解离常数Kd）、FEV1/FVC比值以及血浆皮质醇水平。在对照组和哮喘组中，受体数量（Bmax）均存在显著的昼夜变化，且这种变化在使用沙丁胺醇治疗后并未消除。两组似乎都通过增加受体亲和力来补偿因服用沙丁胺醇而导致的受体数量减少。对于药物/时间的可比组合，对照组和哮喘组之间没有显著差异。我们得出结论，哮喘患者中观察到的“晨降”现象不能简单地用细胞受体数量或亲和力的变化来解释，因为我们的结果表明两组的β - 肾上腺素能受体功能都是完整的。然而，我们对正常昼夜节律的观察结果对未来哮喘患者β - 肾上腺素能受体的研究具有重要意义。
