Circadian variation in number and affinity of beta 2-adrenoceptors in lymphocytes of asthmatic patients.
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.
D000420:Albuterol / Q000627:therapeutic use; D001249:Asthma / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D002940:Circadian Rhythm; D005541:Forced Expiratory Volume; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism*; D010366:Peak Expiratory Flow Rate; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D014797:Vital Capacity
D011943:Receptors, Adrenergic, beta; D000420:Albuterol; D006854:Hydrocortisone