Barnes P J
Department of Thoracic Medicine, National Heart and Lung Institute, London, England.
Life Sci. 1993;52(26):2101-9. doi: 10.1016/0024-3205(93)90725-i.
Although the bronchodilator action of beta 2-adrenoceptor agonists in asthma is largely due to relaxation of airway smooth muscle, these agents have other effects which may contribute to their anti-asthma action. Human airway smooth muscle contains only beta 2-receptors which, when stimulated, stimulate a rise in intracellular cAMP and activation of PKA (protein kinase A), which in turn phosphorylates several cellular proteins, resulting in relaxation. However, beta-agonists also influence membrane K+ channels and induce smooth muscle relaxation without a rise in cAMP, and this mechanism appears to be the major feature of bronchodilatation in asthma. There is also evidence that beta-agonists may modulate neurotransmission in airways via prejunctional receptors on airway nerves, both sensory and motor. Blockade of prejunctional beta 2-receptors in asthma patients may lead to marked rise in acetylcholine release, with severe bronchoconstriction. Although beta-agonists have little or no effect on the chronic inflammatory response which underlies chronic airway hyper-responsiveness, they do inhibit the release of histamine from mast cells in vitro. The presence of beta-receptors has also been detected not only on mast cells but also on eosinophils, macrophages, lymphocytes and neutrophils, but beta-agonists have little or no inhibitory action on the activities of all these cells due to rapid tachyphylaxis.
虽然β2肾上腺素能受体激动剂在哮喘中的支气管扩张作用主要归因于气道平滑肌的松弛，但这些药物还有其他作用，可能有助于其抗哮喘作用。人气道平滑肌仅含有β2受体，受到刺激时，会刺激细胞内cAMP升高并激活蛋白激酶A（PKA），PKA进而使几种细胞蛋白磷酸化，导致平滑肌松弛。然而，β激动剂也会影响膜钾通道，并在不引起cAMP升高的情况下诱导平滑肌松弛，这一机制似乎是哮喘中支气管扩张的主要特征。也有证据表明，β激动剂可能通过气道神经（包括感觉神经和运动神经）上的节前受体调节气道中的神经传递。哮喘患者节前β2受体的阻断可能导致乙酰胆碱释放显著增加，并伴有严重的支气管收缩。虽然β激动剂对慢性气道高反应性所基于的慢性炎症反应几乎没有影响，但它们在体外确实能抑制肥大细胞释放组胺。不仅在肥大细胞上，而且在嗜酸性粒细胞、巨噬细胞、淋巴细胞和中性粒细胞上也检测到了β受体的存在，但由于快速耐受性，β激动剂对所有这些细胞的活性几乎没有抑制作用。
