Kapilevich L V, Kovalev I V, Baskakov M B, Medvedev M A
Siberian Medical University, Tomsk.
Usp Fiziol Nauk. 2001 Apr-Jun;32(2):88-98.
The research of mechanisms of a regulation electrical and contractile of properties of unstriated muscles of an internals remains by an actual problem of modern physiology and medicine. Already now it is possible to state that the efficacy of means of correction of distresses of an internals depends on a degree of a level of scrutiny of these mechanisms. Among physiologically active substances effecting on smooth muscle cells (SM), the special relaxing factor synthesized by endotheliocytes, epithelial cells and SM. Identified by the majority of the explorers as oxide of nitrogen (NO), relaxing factor responds for exhibiting of many myogenic responses of pots and pneumatic routes. The mechanisms of synthesis and implementation of effects of this factor in SM cells up to the extremity are not clarified. The considerable advance in learning mechanisms of operation relaxing factor on SM is connected to discovering of ability of some nitro compounds to replicate NO-dependent relaxing effects in these cells. The main systems of intracellular regulation are involved in mechanisms of implementation endothelial and epithelial local regulatory effects on SM. The majority of the explorers bind an epithelium-dependent release phenomenon SM to an activation of a solvable fraction guanilatcyclase, found in the majority of cells, and effects of cGMP-dependent protein kinases. There are reports on ability of inhibitors NO-sintase to depress a release phenomenon SM of pots and bronchuses, about dependence of a mechanical strain SM of pots and respiratory tract from a contents cGMP in cells. However there are datas giving establishments to guess, that alongside with guanilatciclase in a release phenomenon SM, induced relaxing factors or nitro compounds, the immediate involvement is accepted by cAMP-dependent protein kinases. The most probable point of interaction cAMP and cGMP-dependent processes is phospodiesterase of cyclic nucleotides. It citosolium the enzyme labilized by calmodulin, is capable to carry out a hydrolysis of both cyclic nucleotides, and the affinity native phospodiesterase to cGMP exceeds affinity to cAMP more, than on the order. It is impossible to eliminate immediate interference of NO-dependent processes in a regulation of activity contractile proteins. The ability cGMP-dependent processes to depressing mechanisms of phosphorylation and intensifying of a dephosphorylization of contraktion proteins SM is shown. At these processes can variate and affinity of the acto-miosin complex to ions of calcium, producing a release phenomenon of smooth muscles. On all visibility, production relaxing of the factor and the implementation is epithelial and endothelium-SM of mutual relation in a respiratory tract and pots comes true by modulating influence at the calcium signal system of other systems. For example, production relaxing of the factor by an epithelium and endothelium, being calcium-dependent process, is regulated at involvement calmodulin-similar Ca(2+)-connecting proteins and protein kinase C. Control of tone SM through change of membrane potential relaxing factor carries out by paravariation of potassium conduction of a membrane SM, and, is more probable than all through calcium-dependent and ATP-sensitive components. Potencial-dependent control of a muscle tone comes true through change of efficacy of an operation from a branch of the calcium signal system and calcium pompes at submaximal concentrations of free calcium in citosolium.
内脏平滑肌电特性和收缩特性的调节机制研究仍然是现代生理学和医学的一个实际问题。现在已经可以指出,纠正内脏功能紊乱手段的疗效取决于对这些机制的研究水平。在对平滑肌细胞(SM)有作用的生理活性物质中,由内皮细胞、上皮细胞和SM合成的特殊舒张因子。大多数研究者认为该舒张因子为一氧化氮(NO),它介导了许多血管和气道的肌源性反应。该因子在SM细胞中直至末梢的合成及作用机制尚未阐明。在了解舒张因子对SM的作用机制方面取得的重大进展与发现一些硝基化合物能够在这些细胞中复制NO依赖性舒张效应有关。细胞内调节的主要系统参与了内皮和上皮对SM的局部调节作用机制。大多数研究者将SM的上皮依赖性释放现象与大多数细胞中发现的可溶性鸟苷酸环化酶的激活以及cGMP依赖性蛋白激酶的作用联系起来。有报道称NO合酶抑制剂能够抑制血管和支气管的SM释放现象,血管和呼吸道的SM机械张力依赖于细胞内cGMP的含量。然而,有数据使人推测,在由舒张因子或硝基化合物诱导的SM释放现象中,除了鸟苷酸环化酶外,cAMP依赖性蛋白激酶也直接参与其中。cAMP和cGMP依赖性过程最可能的相互作用点是环核苷酸磷酸二酯酶。它是一种被钙调蛋白不稳定化的胞质酶,能够水解两种环核苷酸,并且天然磷酸二酯酶对cGMP的亲和力比对cAMP的亲和力高出一个数量级以上。不可能排除NO依赖性过程对收缩蛋白活性调节的直接干扰。已显示cGMP依赖性过程能够抑制SM收缩蛋白的磷酸化机制并增强其去磷酸化。在这些过程中,肌动球蛋白复合物对钙离子的亲和力可能会发生变化,从而产生平滑肌的释放现象。显然,该因子的产生和作用是通过对其他系统钙信号系统的调节影响,实现呼吸道和血管中上皮与内皮 - SM之间的相互关系。例如,上皮和内皮产生舒张因子这一钙依赖性过程,是通过钙调蛋白样Ca(2+)结合蛋白和蛋白激酶C的参与来调节的。舒张因子通过改变SM膜的钾传导来控制SM的张力,并且很可能是通过钙依赖性和ATP敏感性成分来实现的。肌肉张力的电位依赖性控制是通过在胞质中游离钙亚最大浓度下改变钙信号系统分支和钙泵的作用效率来实现的。