Effects of β_2-adrenoceptor agonists on anti-IgE-induced contraction and smooth muscle reactivity in human airways

摘要

1. The β_2-adrenoceptor agonists, salbutamol, salmeterol and RP 58802 relaxed basal tone of human isolated bronchial smooth muscle. Salmeterol- and RP 58802-induced relaxations persisted for more than 4 h when the medium was constantly renewed after treatment. 2. Salbutamol, salmeterol and RP 58802 reversed histamine-induced contractions in human airways (pD_2 values: 6.15 ±0.21, 6.00 ± 0.19 and 6.56 ±0.12, respectively). 3. Anti-IgE-induced contractions were significantly inhibited immediately after pretreatment of preparations with β_2-adrenoceptor agonists (10 μM). However, when tissues were treated with β_2-agonists and then washed for a period of 4 h, salmeterol was the only agonist which significantly inhibited the anti-IgE response. 4. Histamine response curves were shifted to the right immediately after pretreatment of tissues with the β_2-adrenoceptor agonists (10 μM; 20 min), but maximal contractions were not affected. After a 4h washing period, the histamine curves were not significantly different from controls. Concentration-effect curves to acetylcholine (ACh) or leukotriene C_4 (LTC_4) were not significantly modified after β_2-agonist pretreatment. 5. These results suggest that β_2-adrenoceptor agonists may prevent anti-IgE-induced contraction by inhibition of mediator release rather than alterations of those mechanisms involved in airway smooth muscle contraction.