Vascular Smooth Muscle Cell Signaling Mechanisms for Contraction to Angiotensin II and Endothelin-1.
Vascular Smooth Muscle Cell Signaling Mechanisms for Contraction to Angiotensin II and Endothelin-1.
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DOI：
10.1016/j.jash.2008.09.002
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Webb RC
中科院分区：
文献类型：
--
作者：
Wynne BM;Chiao CW;Webb RC
血管活性肽，如内皮素-1和血管紧张素II是由位于靶细胞细胞膜上的特定受体蛋白识别的。在受体识别之后，细胞反应的特异性是通过g蛋白偶联配体结合来调节细胞内效应物来实现的。这些细胞内效应物将是这篇关于内皮素-1和血管紧张素II引发的收缩活性的简要综述的主题。平滑肌细胞中的内皮素-1和血管紧张素II激活受体，导致磷脂酶C （PLC）激活，导致第二信使肌醇三磷酸（IP3）和二酰基甘油（DAG）的产生。IP3刺激胞内Ca2+从肌浆网释放，DAG引起蛋白激酶C （PKC）激活。此外，不同的Ca2+进入通道，如电压操作（VOC），受体操作（ROC）和存储操作（SOC） Ca2+通道，以及Ca2+渗透性非选择性阳离子通道（NSCC），都参与细胞内Ca2+浓度的升高。细胞内Ca2+的升高是短暂的，并通过Ca2+-钙调蛋白相互作用启动收缩活动，刺激肌球蛋白轻链（MLC）磷酸化。当Ca2+浓度开始下降时，收缩蛋白的Ca2+敏化通过RhoA/ rho激酶途径来抑制MLC磷酸酶（MLCP）的去磷酸化，从而维持力的产生。从细胞质中去除Ca2+和刺激MLCP启动平滑肌松弛过程。在高血压等病理情况下，这些细胞信号成分的改变可导致过度刺激状态，导致血管持续收缩和血压升高。
Vasoactive peptides, such as endothelin-1 and angiotensin II are recognized by specific receptor proteins located in the cell membrane of target cells. Following receptor recognition, the specificity of the cellular response is achieved by G-protein coupling of ligand binding to the regulation of intracellular effectors. These intracellular effectors will be the subject of this brief review on contractile activity initiated by endothelin-1 and angiotensin II. Activation of receptors by endothelin-1 and angiotensin II in smooth muscle cells results in phopholipase C (PLC) activation leading to the generation of the second messengers insitol trisphosphate (IP3) and diacylglycerol (DAG). IP3 stimulates intracellular Ca2+ release from the sarcoplasmic reticulum and DAG causes protein kinase C (PKC) activation. Additionally, different Ca2+ entry channels, such as voltage-operated (VOC), receptor-operated (ROC), and store-operated (SOC) Ca2+ channels, as well as Ca2+-permeable nonselective cation channels (NSCC), are involved in the elevation of intracellular Ca2+ concentration. The elevation in intracellular Ca2+ is transient and initiates contractile activity by a Ca2+-calmodulin interaction, stimulating myosin light chain (MLC) phosphorylation. When the Ca2+ concentration begins to decline, Ca2+-sensitization of the contractile proteins is signaled by the RhoA/Rho-kinase pathway to inhibit the dephosphorylation of MLC phosphatase (MLCP) thereby maintaining force generation. Removal of Ca2+ from the cytosol and stimulation of MLCP initiates the process of smooth muscle relaxation. In pathological conditions such as hypertension, alterations in these cellular signaling components can lead to an over stimulated state causing maintained vasoconstriction and blood pressure elevation.
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影响因子：
19.6
作者：
COFFMAN, TM;HIMMELSTEIN, S;KLOTMAN, PE
通讯作者：
KLOTMAN, PE
DOI：
10.1073/pnas.86.10.3915
发表时间：
1989-05-01
影响因子：
11.1
作者：
GOTO, K;KASUYA, Y;MASAKI, T
通讯作者：
MASAKI, T
DOI：
10.1152/ajpheart.1997.272.1.h130
发表时间：
1997-01-01
影响因子：
4.8
作者：
HilalDandan, R;Ramirez, MT;Brunton, LL
通讯作者：
Brunton, LL
影响因子：
4.5
作者：
Bouallegue, Ali;Daou, Grace Bou;Srivastava, Ashok K.
通讯作者：
Srivastava, Ashok K.
影响因子：
5.6
作者：
Chitaley, K;Weber, D;Webb, R C
通讯作者：
Webb, R C