Mechanism of cyclic-GMP-dependent relaxation in vascular smooth muscle.
Mechanism of cyclic-GMP-dependent relaxation in vascular smooth muscle.
复制标题
血管平滑肌环鸟苷酸依赖性松弛机制。
DOI：
10.1042/bst0160497
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发表时间：
1988
影响因子：
3.9
通讯作者：
Johnson,RM
中科院分区：
文献类型：
--
作者：
Lincoln,TM;Cornwell,TL;Rashatwar,SS;Johnson,RM
环GMP是控制血管平滑肌张力的主要因素之一。已经证实，几种血管扩张药物，特别是硝基甘油和硝普苷等氮氧化物血管扩张药物，可以刺激平滑肌环GMP含量的增加（lgnarro & Kadowitz, 1985; Waldman & Murad, 1987）。此外，环GMP的类似物在微摩尔浓度下产生弛豫。最近，一些生理上重要的血管平滑肌张力调节因子，特别是内皮源性松弛因子（EDRF）和心房利钠因子（ANF），被发现可以刺激环状GMP的形成（Holtzman, 1983; Winquist et af., 1984）。由于其在血管功能和血流调节中的关键作用，人们对环GMP在细胞中产生有生理意义的反应的方式重新产生了兴趣。在平滑肌中，环GMP的主要受体蛋白是环GMP依赖性蛋白激酶。该蛋白已被纯化、表征和测序，但其生理作用仍然未知（Lincoln & Corbin, 1983）。显然，在细胞中识别出响应环GMP升高的磷酸化蛋白将有助于我们理解环GMP在平滑肌中的作用机制。然而，到目前为止，还没有这样的蛋白质被鉴定和表征。因此，为了确定环GMP和环GMP依赖性蛋白激酶在平滑肌中的作用，有必要首先确定环GMP的作用部位。我们对平滑肌功能调节的理解相当先进的一个领域是平滑肌收缩的生物化学。一般认为，平滑肌肌球蛋白（MLC） 20000 Da轻链的磷酸化是通过Ca2+-calmodulindependent activation of myosin light chain kinase （MLCK）实现的。
It has become evident that cyclic GMP is one of the major factors controlling vascular smooth muscle tone. It is well established that several vasodilator drugs, particularly the nitrogen oxide vasodilator drugs such as nitroglycerine and nitroprusside, stimulate increases in smooth muscle cyclic GMP content (lgnarro & Kadowitz, 1985; Waldman & Murad, 1987). Furthermore, analogues of cyclic GMP produce relaxation at micromolar concentrations. More recently, several physiologically important regulators of vascular smooth muscle tone, notably the endothelialderived relaxing factor (EDRF) and atrial natriuretic factor (ANF), have been found to stimulate cyclic GMP formation (Holtzman, 1983; Winquist et af., 1984). Because of its pivotal role in the regulation ot vascular function and blood flow, there has been a renewed interest in the manner in which cyclic GMP acts in cells to produce physiologically meaningful responses. In smooth muscle, the major receptor protein for cyclic GMP is the cyclic-GMP-dependent protein kinase. This protein has been purified, characterized and sequenced, yet its physiological role is still unknown (Lincoln & Corbin, 1983). Obviously, the identification of proteins which are phosphorylated in the cell in response to cyclic GMP elevations would contribute to our understanding of the mechanism of action of cyclic GMP in smooth muscle. However, no such proteins have been identified and characterized to date. Therefore, to define the role of cyclic GMP and the cyclic-GMP-dependent protein kinase in smooth muscle, it would appeal necessary to first identify the site of action of cyclic GMP. One area where our understanding of the regulation of smooth muscle function is considerably advanced is in the biochemistry of smooth muscle contraction. It is generally accepted that phosphorylation of the 20000 Da light chain of smooth muscle myosin (MLC) by the Ca2+-calmodulindependent activation of myosin light chain kinase (MLCK)