Wynne Brandi M, Chiao Chin-Wei, Webb R Clinton
Medical College of Georgia, Augusta, GA 30912.
J Am Soc Hypertens. 2009 Mar-Apr;3(2):84-95. doi: 10.1016/j.jash.2008.09.002.
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 (IP(3)) and diacylglycerol (DAG). IP(3) stimulates intracellular Ca(2+) release from the sarcoplasmic reticulum and DAG causes protein kinase C (PKC) activation. Additionally, different Ca(2+) entry channels, such as voltage-operated (VOC), receptor-operated (ROC), and store-operated (SOC) Ca(2+) channels, as well as Ca(2+)-permeable nonselective cation channels (NSCC), are involved in the elevation of intracellular Ca(2+) concentration. The elevation in intracellular Ca(2+) is transient and initiates contractile activity by a Ca(2+)-calmodulin interaction, stimulating myosin light chain (MLC) phosphorylation. When the Ca(2+) concentration begins to decline, Ca(2+)-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 Ca(2+) 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.
血管活性肽，如内皮素 -1 和血管紧张素 II，可被位于靶细胞膜上的特定受体蛋白识别。受体识别后，通过配体结合的 G 蛋白偶联来调节细胞内效应器，从而实现细胞反应的特异性。这些细胞内效应器将成为本简短综述关于内皮素 -1 和血管紧张素 II 引发的收缩活动的主题。内皮素 -1 和血管紧张素 II 在平滑肌细胞中激活受体导致磷脂酶 C（PLC）活化，进而产生第二信使肌醇三磷酸（IP(3)）和二酰甘油（DAG）。IP(3) 刺激肌浆网释放细胞内 Ca(2+)，DAG 导致蛋白激酶 C（PKC）活化。此外，不同的 Ca(2+) 进入通道，如电压门控（VOC）、受体门控（ROC）和储存门控（SOC）Ca(2+) 通道，以及 Ca(2+) 通透的非选择性阳离子通道（NSCC），都参与细胞内 Ca(2+) 浓度的升高。细胞内 Ca(2+) 的升高是短暂的，并通过 Ca(2+)-钙调蛋白相互作用引发收缩活动，刺激肌球蛋白轻链（MLC）磷酸化。当 Ca(2+) 浓度开始下降时，收缩蛋白的 Ca(2+) 敏化由 RhoA/Rho 激酶途径发出信号，以抑制 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 Ca(2+) 并刺激 MLCP 启动平滑肌舒张过程。在高血压等病理状态下，这些细胞信号成分的改变可导致过度刺激状态，引起持续的血管收缩和血压升高。
