Effects of β2‐agonist‐ and dexamethasone‐treatment on relaxation and regulation of β‐adrenoceptors in human bronchi and lung tissue

• Published in: British journal of pharmacology 1997-08, Vol.121 (8), p.1523-1530
• Main Authors: Hauck, R. W., Harth, M, Schulz, C, Präuer, H, Böhm, M, Schömig, A
• Format: Article
• Language: English
• Subjects: aminophylline; asthma; Biological and medical sciences; corticosteroid; desensitization; down‐regulation; Drug toxicity and drugs side effects treatment; Human bronchi; human lung parenchyma; isoprenaline, dexamethasone; Medical sciences; Pharmacology. Drug treatments; Toxicity: respiratory system, ent, stomatology; β‐adrenoceptor agonist
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0701289

1 Long‐term treatment with β2‐adrenoceptor agonists can lead to a decreased therapeutic efficacy of bronchodilatation in patients with obstructive pulmonary disease. In order to examine whether or not this is due to β‐adrenoceptor desensitization, human bronchial muscle relaxation was studied in isolated bronchial rings after pretreatment with β2‐adrenoceptor agonists. Additionally, the influence of pretreatment with dexamethasone on desensitization was studied. 2 The effect of β2‐agonist incubation alone and after coincubation with dexamethasone on density and affinity of β‐adrenoceptors was investigated by radioligand binding experiments. 3 In human isolated bronchi, isoprenaline induces a time‐ and concentration‐dependent β‐adrenoceptor desensitization as judged from maximal reduction in potency by a factor of 7 and reduction of 73±4% in efficacy of isoprenaline to relax human bronchial smooth muscle. 4 After an incubation period of 60 min with 100 μmol l−1 terbutaline, a significant decline in its relaxing efficacy (81±8%) and potency (by a factor 5.5) occurred. 5 Incubation with 30 μmol l−1 isoprenaline for 60 min did not impair the maximal effect of a subsequent aminophylline response but led to an increase in potency (factor 4.4). 6 Coincubation of dexamethasone with isoprenaline (120 min; 30 μmol l−1) preserved the effect of isoprenaline on relaxation (129±15%). 7 In radioligand binding experiments, pretreatment of lung tissue for 60 min with isoprenaline (30 μmol l−1) resulted in a decrease in β‐adrenoceptor binding sites (Bmax) to 64±1.6% (P