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

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 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.

Specific Immunological Modulation of Lymphocyte Adenylate Cyclase in Asthmatic Patients after Allergenic Bronchial Provocation

“…This was also concluded by several other investigators who found normal beta-adrenergic responses or beta-adrenergic receptor numbers in leukocytes of asthmatic patients [8-11, 21, 22]. In some of these studies, a reduced beta-adrenergic receptor function or number was only found after treatment of the patients with betaadrenergic bronchodilator drugs [8][9][10][11]21], However, our observation that reduced beta-adrenergic respon siveness may also be acquired after an allergen-in duced asthmatic reaction could explain that reduced beta-adrenergic responses or reduced beta-adrenergic receptor numbers are sometimes found in leukocytes from untreated patients, especially during active and severe symptoms [2,[4][5][6],…”

Circadian Characteristics of Urinary Leukotriene E4 in Healthy Subjects and Nocturnal Asthmatic Patients

“…In general, catecholamines, corticosteroids, vagal tone, inflammatory mediators, mucociliary clearance, and ␤ 2 -agonist responsiveness have all been shown to strengthen the potential for nocturnal exacerbation. [17][18][19] Urinary adrenaline or noradrenaline, and plasma histamine have been correlated to morning dips in peak expiratory flow rate (PEFR). 17,18 Nocturnal asthma is associated with a significant increase of both eosinophils in BAL fluid 8 and eosinophils and macrophages in the alveolar tissue at 4 am.…”

?-Adrenoceptor density and resolution of high and low affinity state on B- and T-cells in asthmatic and non-asthmatic children

“…These problems are based upon the observation that the 13-adrenoceptor function may vary with the age of the patients [16], the circadian rhythm [20], a drug therapy with 13-sympathicomimetics or glucocorticosteroids [15], the disease state itself or additional viral or bacterial infections [17]. The possibility of a different receptor density and affinity state in B-and T-cells may lead to a misinterpretation in the case of a changed distribution of these cells in asthmatic disease [1,14].…”