Airway smooth muscle and asthma.
Airway smooth muscle and asthma.
复制标题
气道平滑肌和哮喘。
DOI：
10.1165/ajrcmb/7.6.565
复制
发表时间：
1992
影响因子：
6.4
通讯作者：
deLanerolle,P
中科院分区：
文献类型：
--
作者：
deLanerolle,P
" Asthma morbidity and mortality are on the rise. From 1980 to 1987, the prevalence rate of asthma in the United States increased 29 percent, and death rates for asthma as the firstlisted diagnosis increased 31 percent. In 1988, asthmarelated health care expenditures exceeded $4 billion in the United States"(1). Nevertheless, apart from understanding that bronchodilators are effectivein treating asthmatic symptoms, we know little about the underlying mechanisms at the molecular level in asthma. One reason for this is that asthma is a syndrome that involves multiple tissues (eg, mast cells, neutrophils, epithelial cells, smooth muscles) and the interactions between these tissues. In addition, a number of hormones, nerves, and neurotransmitters can affect these cells and their interactions.In light of the central role of airway smooth muscle in asthma, a great deal of research has focused on understanding the molecular basis of the regulation of smooth muscle contraction and whether there are alterations in these regulatory mechanisms in asthma. Intense research effortsover the past 15 years have clearly demonstrated that the regulation of smooth muscle contraction involves the phosphorylation of the 20 kD light chain subunit of smooth muscle myosin (MLC20). Biochemical experiments' have demonstrated that the transfer of the terminal phosphate group from ATP to ser 19 on MLC20, with the subsequent formation of a phosphoester bond, results in the stimulation of the actin-activated ATPase activity of smooth muscle myosin (2). Other studies have shown that the enzyme catalyzing this phosphorylation reaction, myosin light chain kinase (MLCK), is a calciumcalmodulin-dependent enzyme (2). Based on these studies, the following sequence of events was postulated to occur during smooth muscle contraction:(1) an increase in intracellular calcium results in the binding of calcium to calmodulin;(2) the calcium-calmodulin complex then binds to and activates MLCK;(3) the active enzyme phosphorylates MLC20;(4) the phosphorylated myosin interacts with actin to hydrolyze ATP;(5) the energy released following the hydrolysis of ATP is used to move
