Circadian Variation in Number and Affinity of β2-Adrenoceptors in Lymphocytes of Asthmatic Patients

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Abstract
To determine whether circadian variation in adrenoceptor function might underlie the morning dip in peak expiratory flow (PEF) rate and its abolition by salbutamol, indices of .beta.-adrenoceptor function (.beta.max [maximum binding], and Kd), the ratio FEV1[forced expiratory volume in 1 s]/FVC [forced vital capacity] and plasma cortisol at 0800 and 1800 h on and off salbutamol (4 mg given orally every 4 h) in 5 extrinsic asthmatic patients and 5 normal volunteers. There was a significant circadian variation in receptor numbers (.beta.max) 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. The morning dip observed in asthmatic patients evidently cannot simply be explained by changes in cell receptor number or affinity, since both groups apparently have intact .beta.-adrenoceptor function. Observations of the normal circadian rhythm has important implications for future studies of .beta.-adrenoceptors in asthmatic patients.