Department of Physiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Front Biosci (Landmark Ed). 2010 Jan 1;15(2):750-64. doi: 10.2741/3644.
Airway smooth muscle cell (ASMC) contraction is regulated by myosin phosphorylation to control actin-myosin cross-bridge activity. Myosin phosphorylation is determined by the antagonistic activity of myosin light chain (MLC) kinase (MLCK) and phosphatase (MLCP). MLCK activity is increased by increases in intracellular Ca2+ concentration ([Ca2+]i) associated with Ca2+ oscillations. MLCP activity is decreased by phosphorylation of MLCP or accessory proteins by kinases, including Rho-kinase or protein kinase C. During agonist-induced ASMC contraction, these 2 pathways are simultaneously activated. Because MLCP activity is often independent of [Ca2+]i, changes in MLCP activity can alter ASMC tone at a constant [Ca2+]i; a behavior termed Ca2+ sensitivity. In asthma, airway hyperresponsiveness (AHR) may result from an increase in the Ca2+-dependent contractile mechanisms and/or the Ca2+ sensitivity of ASMCs. Conversely, inhalation of beta2-adrenergic agonists induce airway relaxation by simultaneously slowing the Ca2+ oscillations and reducing the Ca2+ sensitivity of ASMCs. However, the action of beta2-adrenergic agonists varies with species. Consequently, the development of beta2-adrenergic agonists requires a characterization of their action in human airways.
气道平滑肌细胞（ASMC）的收缩受肌球蛋白磷酸化调节，以控制肌动球蛋白交联桥的活性。肌球蛋白磷酸化由肌球蛋白轻链激酶（MLCK）和磷酸酶（MLCP）的拮抗活性决定。细胞内 Ca2+浓度（[Ca2+]i）增加与 Ca2+振荡相关，导致 MLCK 活性增加。MLCP 活性通过 Rho 激酶或蛋白激酶 C 等激酶对 MLCP 或辅助蛋白的磷酸化而降低。在激动剂诱导的 ASMC 收缩过程中，这两种途径同时被激活。由于 MLCP 活性通常与 [Ca2+]i 无关，因此 MLCP 活性的变化可以在恒定的 [Ca2+]i 下改变 ASMC 的张力；这种行为称为 Ca2+敏感性。在哮喘中，气道高反应性（AHR）可能是由于依赖 Ca2+的收缩机制增加和/或 ASMCs 的 Ca2+敏感性增加所致。相反，β2-肾上腺素能激动剂的吸入通过同时减缓 Ca2+振荡并降低 ASMCs 的 Ca2+敏感性来诱导气道松弛。然而，β2-肾上腺素能激动剂的作用因物种而异。因此，β2-肾上腺素能激动剂的开发需要对其在人类气道中的作用进行表征。
