Abstract：
Classically, the effects elicited by corticosteroids (CS) are mediated by the binding and activation of cytosolic glucocorticoid receptors (GR). However, several of the non-genomic effects of CS seem to be mediated by putative non-classic membrane receptors characterized by pharmacological properties that are different from those of classic cytosolic GR. Since pre-clinical findings suggest that inhaled CS (ICS) may also regulate the bronchial contractile tone via putative CS membrane-associate receptors, the aim of this review was to systematically report and discuss the impact of CS on human airway smooth muscle (ASM) contractility and airway hyperresponsiveness (AHR). Current evidence indicates that CS have significant genomic/non-genomic beneficial effects on human ASM contractility and AHR, regardless of their anti-inflammatory effects. CS are effective in reducing either the expression, synthesis or activity of α-actin, CD38, inositol phosphate, myosin light chain kinase, and ras homolog family member A in response to several pro-contractile stimuli; overall these effects are mediated by the genomic action of CS. Moreover, CS elicited a strong bronchorelaxant effect via the rapid activation of the Gsα-cyclic-adenosine-monophosphate-protein-kinase-A pathway in hyperresponsive airways. The possibility of modulating the dose of the ICS in a triple ICS/long-acting β2-adrenoceptor agonist/long-acting muscarinic antagonist fixed-dose combination supports the use of a Triple MAintenance and Reliever Therapy (TriMART) in those asthmatic patients at Step 3-5 who may benefit from a sustained bronchodilation and have been suffering from an increased parasympathetic tone.
摘要：
经典的,皮质类固醇（CS）引起的作用是通过细胞溶质糖皮质激素受体（GR）的结合和激活介导的。然而,CS的几种非基因组效应似乎是由推定的非经典膜受体介导的，其药理特性不同于经典的胞浆GR。由于临床前研究结果表明，吸入CS（ICS）也可能通过推定的CS膜相关受体调节支气管收缩张力，本综述旨在系统报告和讨论CS对人类气道平滑肌(ASM)收缩力和气道高反应性(AHR)的影响.目前的证据表明，CS对人类ASM收缩性和AHR具有显著的基因组/非基因组有益作用，不管他们的抗炎作用。CS有效地减少了表达，α-肌动蛋白的合成或活性，CD38，肌醇磷酸，肌球蛋白轻链激酶，和ras同源物家族成员A对几种促收缩刺激的反应；总体而言，这些作用是由CS的基因组作用介导的。此外，CS通过快速激活高反应气道中的Gsα-环腺苷-单磷酸-蛋白激酶-A途径引起强烈的支气管舒张作用。在三联ICS/长效β2-肾上腺素受体激动剂/长效毒蕈碱拮抗剂固定剂量组合中调节ICS剂量的可能性支持在步骤3-5的哮喘患者中使用三联强化和缓解疗法（TriMART），这些患者可能受益于持续的支气管扩张并患有副交感神经张力增加。
